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Ozone Therapy and Long COVID: What the Research Shows (2026 Update)

Long COVID and ME/CFS look different on paper - one follows a named virus, the other has many triggers - but people who live with them describe the same thing: exhaustion that rest does not fix, a crash after doing too much, poor sleep, aching muscles and a foggy head. Over the last three years, researchers have started finding the same things in the blood and muscle of both groups. This page sets out what they found, what happened when ozone therapy was tried, and why the two might be connected.

Five studies have now tested ozone therapy in long COVID, and one used the same route people use at home. All five reported less fatigue and better function. None was placebo-controlled, so the evidence is early - but it points in one direction.

Updated September 2026. This page replaces our July 2024 article on the same question and adds four studies published since.

What long COVID and ME/CFS have in common

Four findings keep turning up in patients with either condition. They matter here because each one is something ozone therapy has been shown to act on - in other people, in other conditions. We come back to that below.

1

Oxidative stress

A US research team measured higher oxidative stress in the immune cells of 27 people with ME/CFS and 20 with long COVID than in 25 healthy controls. Women with ME/CFS were also less able to clear reactive oxygen species.1

2

Mitochondria under-performing

Muscle biopsies from 25 long COVID patients showed a lower capacity to make energy than 21 controls - and it was worse the day after exercise, which is the crash patients describe.2

3

Stiffer, misshapen red blood cells

In 30 long COVID patients, one red cell in five was abnormally shaped, against one in thirty-five in controls, and the cells clumped more. The more abnormal cells, the worse the fatigue.3 Stiffer red cells were reported in ME/CFS in 2019.4

4

A shifted gut microbiome

Stool samples from 76 people with ME/CFS and 50 with long COVID showed the same depletion of certain beneficial bacteria compared with 37 controls. The shifts tracked fatigue, not gut symptoms.5

A fifth thread runs through all of these: the lining of the blood vessels. A 2026 review argues that viral infection can push these cells into a worn-out, inflammatory state, and that this explains the reduced blood flow to brain and muscle seen in both conditions.6

What happened when ozone therapy was tried

Five published studies have given ozone to people with long COVID. Here they are in order of strength of design, with the numbers as reported.

RANDOMISED TRIAL - 73 PATIENTS - 2024

Usual care, with or without ozone

A Wuhan University respiratory team randomly assigned long COVID patients to usual care alone or usual care plus ozone autohaemotherapy. Seventy-one per cent of the ozone group had their symptom score at least halved, against 45 per cent on usual care alone. Lung volume, walking distance, inflammatory and clotting markers also improved more with ozone. No adverse effects.7

One of two randomised studies. No sham procedure, so patients knew which group they were in.

RANDOMISED STUDY - 140 PATIENTS - 2025

Medication, with or without ozone

A Crimean team randomly assigned people with post-COVID fatigue syndrome to a course of medication alone or medication plus ten daily infusions of ozonated saline. At 30 days the lipid-damage marker malondialdehyde had fallen 69 per cent with ozone against 39 per cent without; fatigue, insomnia, anxiety and cognition scores all improved more; and 94 per cent of the ozone group were rated free of illness against 63 per cent. No adverse events.8

The only study to measure oxidative stress before and after. No placebo infusion, no blinding.

RECTAL INSUFFLATION - 23 PATIENTS - 2026

The home route, in a clinic

A Spanish university team gave 24 sessions of rectal ozone insufflation over 12 weeks. Grip strength rose from 24.6 kg to 27.7 kg by week six and held. Physical and mental quality-of-life scores both rose significantly. No adverse events of interest across the whole course.9

The first long COVID study to use the route most home users rely on. No control group; the authors call it hypothesis-generating.

RECORDS REVIEW - 40 PATIENTS - 2026

Ten sessions, five questionnaires

A Turkish rehabilitation specialist reviewed the records of post-COVID patients who had completed ten sessions of autohaemotherapy. The median fatigue score fell from 31 to 9.5. Anxiety, depression and sleep improved, and so did eight of nine quality-of-life domains. No adverse events.10

Retrospective, no control group, no follow-up after the course.

CASE SERIES - 100 PATIENTS - 2021

The first report

The Italian group that had already treated ME/CFS with ozone reported on 100 long COVID patients given autohaemotherapy over two to three weeks. Fatigue scores fell by 67 per cent on average, and around 40 per cent reported near-complete recovery of their fatigue.11

Uncontrolled, self-reported, no follow-up.

For ME/CFS itself the picture has not changed since 2021. The same Italian group treated 200 patients with autohaemotherapy and reported the average fatigue score falling from 6.8 to 2.1 on a seven-point scale, with 77.5 per cent showing a clinically meaningful improvement that held at three months.12 No other group has published ME/CFS results, and no controlled trial has been run. We keep a full review of that evidence in our ME/CFS article.

Read together: five long COVID studies, 376 patients, all reporting less fatigue and better function, no safety signals in any of them. Two are randomised, none is placebo-controlled, and all are small. That is enough to take seriously and not enough to call proven.

Why researchers think it helps

Only one of the five studies measured anything about why its patients improved - the 2025 Crimean study, which found oxidative damage fell and antioxidant enzymes rose alongside the symptom gains.8 Beyond that, the four shared findings above each line up with something ozone therapy has been shown to do elsewhere. The right way to present this is one finding at a time, with a clear line between what has been shown and what is being inferred.

Oxidative stress - the strongest link

Low-dose ozone works by triggering a brief, controlled oxidative signal that switches on the cell's own antioxidant defences - glutathione, superoxide dismutase, catalase - through a master switch called Nrf2.13,14 This is not only theory: in two randomised trials using rectal insufflation, one in 60 people with rheumatoid arthritis and one in 101 with diabetic foot, antioxidant enzymes rose and oxidative damage markers fell in the ozone groups.15,16 A 2024 systematic review across arthritis, diabetes and ageing found the antioxidant "repair" side rose by 21 to 140 per cent compared with untreated groups.17 Long COVID and ME/CFS patients have raised oxidative stress and, in some, a reduced ability to clear it.1 The two findings sit on the same axis. The 2025 Crimean study is the first to measure this in post-COVID patients, and found malondialdehyde falling and both antioxidant enzymes rising further with ozone than without.8 One study, unblinded, with a comparison arm on a medication not used here - but it is the first direct test of the link.

Mitochondria

The same 2024 review found that in animal models mitochondria kept their structure after ozone pre-treatment where untreated controls showed damage, and it describes low-dose ozone as a "redox bioregulator" for conditions driven by mitochondrial oxidative stress.17 Long COVID muscle shows exactly that kind of mitochondrial under-performance.2 The ozone evidence here is preclinical and drawn from other conditions; nobody has biopsied long COVID muscle after ozone.

Red blood cells and oxygen delivery

In 27 people with arterial disease, a single ozonated autohaemotransfusion made red cells more flexible, lowered blood viscosity and improved the blood's oxygen release within half an hour.18 In a separate study, oxygen probes placed in muscle showed the most oxygen-starved tissue improved the most after ozone, and was still better 48 hours later.19 Long COVID patients have stiffer, misshapen red cells, and the more of them, the worse the fatigue.3 Again, the patient groups differ: the ozone studies were in arterial disease, not long COVID.

The gut

Rectal insufflation acts first on the bowel, and a 2018 randomised study in 48 people with constipation-predominant IBS found it shifted the gut microbiota towards beneficial species.20 Long COVID and ME/CFS patients share a depletion of beneficial gut bacteria that tracks their fatigue.5 This is the link most specific to the home route, and the one least tested: no long COVID ozone study has looked at the microbiome.

Blood vessel lining

In animal studies ozone raised the enzyme that makes nitric oxide in the vessel lining and recruited the cells that repair it.21 The evidence on this thread is thinner than the others - animal and cell work only - so we give it one sentence.

Doing it at home

Four of the five long COVID studies used a clinic route - autohaemotherapy or an ozonated saline infusion - which needs a clinician. The 2026 Spanish study used rectal insufflation, which does not. The two routes are rated as comparable systemic treatments in the largest evidence review of the field, which drew on more than 47,000 documented rectal insufflation treatments,22 and rectal insufflation is the route most of our customers use. Everything needed to do it at home is in our ozone therapy bundles.

★★★★★

"I contracted Covid for the third time, and really struggled to come back from it. Overwhelming fatigue, musculoskeletal pain and stiffness, no quality sleep, bad IBS... It took me 3 weeks to realise I have all the tools at my disposal! ... My stomach/bowel issues cleared up within about 5 days, my energy levels slowly returned to my normal, and now after 3 weeks of daily RI the stiffness and aching is also subsiding, my sleep is starting to improve too."

Mathilde Noordzij, New Zealand - Wellness Warrior owner, who has lived with ME/CFS since childhood

One customer's experience is not a study, and we present it as what it is. The long COVID studies above are the evidence; this is what it can look like in practice.

Where the evidence is thin

Two 2026 reviews take a cooler view of ozone therapy as a whole. An umbrella review of the randomised-trial meta-analyses rated the certainty of evidence low or very low across every indication it covered - none of which was long COVID.23 A narrative review in Frontiers in Medicine concluded that the mechanisms are plausible but clinical efficacy "has not been conclusively established", and that ozone should be regarded as investigational and adjunctive.24 We agree with the word adjunctive. Nothing on this page is a reason to stop treatment your doctor has prescribed.

The specific gaps for long COVID are these: no placebo-controlled trial; no follow-up beyond twelve weeks; only one study that measured the mechanisms it proposed; and, for ME/CFS, no study at all outside one Italian group.

If you have long COVID or ME/CFS

Both conditions should be diagnosed and managed with a doctor, and post-exertional crashes mean any new routine should start gently. We follow the guidelines of the International Scientific Committee of Ozone Therapy (ISCO3), whose Madrid Declaration sets out the systemic protocols used in the studies above, and we encourage anyone managing a health condition to work alongside their healthcare practitioner. If you want to understand what ozone does in the body before going further, start with How Ozone Therapy Works.

References

  1. Saha AK, et al. Oxidative stress is a shared characteristic of ME/CFS and Long COVID. Proceedings of the National Academy of Sciences 2025. doi:10.1073/pnas.2426564122
  2. Appelman B, et al. Muscle abnormalities worsen after post-exertional malaise in long COVID. Nature Communications 2024. doi:10.1038/s41467-023-44432-3
  3. Grau M, et al. Red blood cell morphology is associated with altered hemorheological properties and fatigue in patients with long COVID. Biology 2024. Full text at PubMed Central
  4. Saha AK, Schmidt BR, Wilhelmy J, et al. Red blood cell deformability is diminished in patients with Chronic Fatigue Syndrome. Clinical Hemorheology and Microcirculation 2019. doi:10.3233/CH-180469
  5. Ivanov IN, et al. Comparative gut microbiome alterations in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID-19 syndrome. Biomedicines 2026;14(6):1183. mdpi.com
  6. Nunes, et al. Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID. Cell Death & Disease 2026. doi:10.1038/s41419-025-08162-2
  7. He Y, Liu X, Zha S, et al. A pilot randomized controlled trial of major ozone autohemotherapy for patients with post-acute sequelae of COVID-19. International Immunopharmacology 2024;139:112673. Read our summary.
  8. Soldatenko AA, Gumenyuk LN. Dynamics of oxidative stress markers and mental status in patients with post-COVID-19 asthenic syndrome: effects of adjunctive systemic ozone therapy. Russian Open Medical Journal 2025;14:e0109. Read our summary.
  9. Sacristan Perez R, Martínez Vivas MJ, Menéndez-Cepero S, et al. Ozone therapy by rectal insufflation in long COVID syndrome: a preliminary study with thermographic evaluation and quality of life measurement. Future Science OA 2026;12(1):2704605. Read our summary.
  10. Kuculmez O. Efficacy of major ozone autohemotherapy in patients with post-COVID syndrome. Frontiers in Medicine 2026;13:1720578. Read our summary.
  11. Tirelli U, Franzini M, Valdenassi L, et al. Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy - preliminary results on 100 patients. European Review for Medical and Pharmacological Sciences 2021. Read our summary.
  12. Tirelli U, Franzini M, Valdenassi L, et al. Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) greatly improved fatigue symptoms when treated with oxygen-ozone autohemotherapy. Journal of Clinical Medicine 2022;11(1):29. Read our summary.
  13. Sagai M, Bocci V. Mechanisms of action involved in ozone therapy: is healing induced via a mild oxidative stress? Medical Gas Research 2011;1:29. Read our summary.
  14. Galiè M, Covi V, Tabaracci G, Malatesta M. The role of Nrf2 in the antioxidant cellular response to medical ozone exposure. International Journal of Molecular Sciences 2019;20:4009. Read our summary.
  15. León Fernández OS, Viebahn-Haensler R, Cabreja GL, et al. Medical ozone increases methotrexate clinical response and improves cellular redox balance in patients with rheumatoid arthritis. European Journal of Pharmacology 2016;789:313-318. Read our summary.
  16. Martínez-Sánchez G, Al-Dalain SM, Menéndez S, et al. Therapeutic efficacy of ozone in patients with diabetic foot. European Journal of Pharmacology 2005;523:151-161. Read our summary.
  17. Viebahn-Haensler R, León Fernández OS. Mitochondrial dysfunction, its oxidative stress-induced pathologies and redox bioregulation through low-dose medical ozone: a systematic review. Molecules 2024;29(12):2738. Read our summary.
  18. Giunta R, Coppola A, Luongo C, et al. Ozonized autohemotransfusion improves hemorheological parameters and oxygen delivery to tissues in patients with peripheral occlusive arterial disease. Annals of Hematology 2001;80:745-748. Read our summary.
  19. Clavo B, Pérez JL, López L, et al. Effect of ozone therapy on muscle oxygenation. Journal of Alternative and Complementary Medicine 2003;9:251-256. Read our summary.
  20. Mallayeva RM. Ozone therapy and gut microbiota in constipation-predominant irritable bowel syndrome. Modern Issues of Biomedicine 2018;2(1):108-114. Read our summary.
  21. Di Filippo C, Luongo M, Marfella R, et al. Oxygen/ozone protects the heart from acute myocardial infarction through local increase of eNOS activity and endothelial progenitor cells recruitment. Naunyn-Schmiedeberg's Archives of Pharmacology 2010. doi:10.1007/s00210-010-0545-2
  22. Viebahn-Hänsler R, León Fernández OS, Fahmy Z. Ozone in medicine: clinical evaluation and evidence classification of the systemic ozone applications, major autohemotherapy and rectal insufflation. Ozone: Science & Engineering 2016;38:322-345. Read our summary.
  23. Cacciatore S, Abbatecola AM, Calvani R, Veronese N. Effectiveness and safety of ozone therapy in humans: an umbrella review of systematic reviews with meta-analyses of randomized controlled trials. Medical Sciences 2026;14(2):289. mdpi.com
  24. Wójcik, et al. Medical ozone: mechanisms, biological effects and clinical evidence - a narrative review. Frontiers in Medicine 2026;13:1859221. doi:10.3389/fmed.2026.1859221

Many of our customers use ozone therapy at home as a complementary part of their wellness routine, alongside the care of their health practitioner.

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