Ozone Treatment for Chronic Fatigue in Long COVID: A Clinical Perspective (2026)
Background
Long COVID affects an estimated 10 to 20 per cent of people infected with SARS-CoV-2 regardless of how severe the infection was, and the authors put the number affected worldwide above 400 million. It is more common in middle-aged women and in people who had more symptoms in the first week of infection. Chronic fatigue is the most frequently reported symptom, with anxiety, depression and insomnia also common. There is no definitive treatment.
The authors are a research group at the San Antonio Catholic University of Murcia in Spain, including the university's Chair of Ozone Therapy and Chronic Pain. Their starting point is a pattern they had already seen in fibromyalgia: a condition with the same core symptoms, a viral trigger in many cases, and an underlying redox imbalance, which several trials had treated with ozone. This article sets out why they think long COVID may respond in the same way, and proposes a study to find out.
Study design
This is a perspective article in Medical Gas Research - a short, referenced argument rather than a report of new data. It draws on the long COVID pathophysiology literature, the fibromyalgia ozone trials, mechanistic work on how ozone acts, and the three clinical studies of ozone in post-COVID patients that the authors could find. It was submitted in May 2025, accepted in September 2025 and published online in July 2026. It is open access.
Findings
What long COVID shares with fibromyalgia and ME/CFS. The authors summarise the leading account of long COVID: an excessive, sustained release of inflammatory cytokines after infection leading to progressive immune dysregulation, with oxidative damage proposed as a persistent element. They note that SARS-CoV-2 can cross the blood-brain barrier, and that hypercoagulability and vascular injury add neurological risk. The symptom picture - fatigue above all, with pain, brain fog, breathlessness and sleep disturbance - and the mechanisms behind it overlap with fibromyalgia and ME/CFS, which the authors say "mark a dualism" worth exploring.
How ozone is thought to act. The article describes systemic ozone as a controlled "micro-oxidation" that modulates the body's antioxidant systems: ozone reacts to produce hydrogen peroxide and lipid oxidation products; most of the peroxide is taken up by red blood cells, which respond by improving oxygen delivery; the lipid products activate the Nrf2 pathway, which switches on antioxidant enzymes such as glutathione peroxidase and superoxide dismutase. The two systemic routes are major blood ozonation (autohaemotherapy) and rectal insufflation.
Safety and contraindications. The authors describe ozone as conventionally considered safe with few adverse effects, most of them related to injection technique rather than the gas itself, with occasional dizziness or mild nausea that passes within hours. They list absolute contraindications: G6PD deficiency, severe hyperthyroidism, blood clotting disorders, and recent cerebral haemorrhage or heart attack. They stress that the effects depend on specific therapeutic concentrations, and that high or inadequate doses may not have the desired effects.
The existing evidence. The authors found three studies of ozone in post-COVID patients. A randomised pilot trial by He and colleagues found ozone autohaemotherapy plus conventional treatment improved symptoms more than conventional treatment alone, with no adverse effects. Tirelli and colleagues reported that 67 per cent of 100 patients given autohaemotherapy recovered normal function with improvement in fatigue, regardless of sex and age. A Russian study by Soldatenko and Gumenyuk in 140 patients reported a significant reduction in oxidative stress and improved mental status in the ozone group, with the authors stating that 95 per cent experienced complete or near-complete resolution of symptoms. From these, the authors conclude that systemic ozone "may be an effective and pathogenically relevant strategy" for outpatient management of post-acute COVID-19 syndrome.
The proposal. The authors propose an open pilot study of ozone by rectal insufflation as an add-on treatment in long COVID, measuring efficacy, tolerability, and biological and thermographic changes.
What the authors concluded
The authors conclude that "the cited literature suggests the need to delve deeper into this area through new experimental studies that can more convincingly justify the relationship between the clinical features associated with this chronic condition and the effects of medical ozone treatment." Their view is that medical ozone could contribute to improving quality of life and benefit the immuno-inflammatory response in people with persistent COVID-19, and that this should be tested.
Limitations of this study
This is a perspective, not a study. It reports no new patients and no new measurements, and it is two pages long. Its value is in setting out the rationale and the state of the evidence in one place; it does not add to that evidence.
Two notes for readers. The study the authors proposed has since been carried out and published - 23 long COVID patients given rectal insufflation over 12 weeks - and we have summarised it separately. And the article describes all three earlier studies as using major blood ozonation; the Russian study in fact used intravenous infusions of ozonated saline, a different systemic route, as our summary of that study sets out.
Long COVID should be diagnosed and managed with a doctor. Anyone considering ozone therapy alongside their care should discuss it with their own GP or specialist.
Related reading
Rectal Ozone Insufflation in Long COVID: A 12-Week Preliminary Study of 23 Patients (2026) - the study this perspective proposed.
Ozonated Saline Added to Medication in Post-COVID Fatigue: A Randomised Study of 140 Patients (2025)
Fatigue in Long COVID Treated with Oxygen-Ozone Autohaemotherapy: 100 Patients
Ozone Therapy as Add-On Treatment in Fibromyalgia by Rectal Insufflation: An Open-Label Pilot Study - the same group's earlier fibromyalgia work.
Ozone Therapy and Long COVID: What the Research Shows (2026 Update)
Sacristán Pérez R, Cabizosu A, Martínez Vivas MJ, Hidalgo Tallón FJ. Ozone treatment for chronic fatigue in patients with long coronavirus disease: a clinical evidence-based perspective. Medical Gas Research. 2026;16(2). Published online 3 July 2026. doi:10.4103/mgr.MEDGASRES-D-25-00155
Many of our customers use ozone therapy at home as a complementary part of their wellness routine, alongside the care of their health practitioner.