Ozone Therapy Side Effects: What Is Common, What Is Rare and What to Watch For

Most ozone therapy side effects are mild and short: a moment of warmth, a mild headache, pain at the needle site or a small bruise. The Madrid Declaration on Ozone Therapy, 4th edition (ISCO3, 2025) says most side effects come from malpractice, meaning the wrong technique, route, concentration or sterile practice [1]. Serious harm in the published reports came mostly from direct intravenous gas injection, poor sterile technique, or invasive injections by poorly trained operators.

This page summarizes what the Madrid Declaration lists, in plain language. It is education, not medical advice. Check with your healthcare provider before starting, especially if you are pregnant, have a heart or bleeding condition, or take blood thinners.

What are the most common side effects?

The Declaration sorts reported side effects by severity, using the US National Institutes of Health grading scale. The mild ones (grades 1 and 2) are the most common [1]:

• A short sensation of warmth, a mild headache, or mild pain during an ozone injection.
• A bruise (hematoma) at the injection site.
• During IV ozone (MAH), when the blood is returned: itching or tingling of the lips and tongue, nausea, a bad taste in the mouth, and in one patient shortness of breath. These were linked to how fast the blood was returned.
• Pain and a vagal reaction (a lightheaded or faint feeling) after a needle stick.
• After ozone injections near the spine: temporary leg numbness or lower back and leg pain that went away on its own, and in a few people mild eye irritation and short-lived shortness of breath.
• After rectal insufflation: belly swelling (bloating) and constipation in some cases.

Tiredness, aches or a flu-like feeling for a day or two after a session are also reported. See Herxheimer reactions and ozone therapy for how to tell a short die-off-type reaction from too much ozone. For the usual effects by route and how long they last, see what to expect after an ozone session.

What are the grades 1 to 5?

The Declaration lists published case reports under five grades. These are individual reports collected over many years, not rates of how often each one happens [1].

Why do serious side effects happen?

The Declaration is clear about the cause. It says most side effects come from malpractice: the technique, the route, the ozone concentration, or a lack of sterile practice. About the invasive procedures, mostly injections, it says the problems come from poor management by the operator. It says all ozone therapy should be given by physicians who are well trained in the method, because most fatal cases came from training that did not follow current recommendations [1].

Direct intravenous injection of ozone gas should never be used. The Declaration says Bocci described at least six deaths from it and that the practice should not be used under any circumstances. Standard IV ozone (MAH) does not do this. It mixes ozone with a measured amount of the person's own blood outside the body, then returns the blood. See IV ozone therapy (MAH).

How rare are serious side effects?

Extremely rare compared with the number of treatments given. The grade 5 list above is a handful of individual case reports collected over many years. Velio Bocci, a physiologist at the University of Siena, wrote that millions of ozonated autohemotherapy (MAH) treatments over about three decades, even those done in an empirical way, produced neither acute nor chronic toxic effects. He added that, according to a survey by Jacobs (1982), autohemotherapy had the lowest number of medical complications [2].

The deaths that were recorded in that paper came from direct intravenous injection of ozone/oxygen gas, an application the European Society of Ozonetherapy has prohibited since 1983 [2]. This is the practice described above as condemned. It is not standard IV ozone (MAH).

Bocci made the same point in a later review, "Is it true that ozone is always toxic? The end of a dogma": the harm comes from breathing ozone, while blood exposed to a small, precisely calculated dose for a few minutes is protected by its own antioxidants [3]. The Madrid Declaration agrees that most side effects, and most fatal cases, are the result of malpractice [1].

How can I lower my risk?

• Use a well-trained provider for any IV or injection method, and ask about their sterile technique.
• Never accept direct IV gas injection.
• Follow measured doses and a written protocol. See the protocols.
• During IV ozone, the blood should be returned slowly. The Declaration links faster return to more symptoms.
• Never breathe ozone gas. See why you can’t breathe ozone.
• Check who should not use ozone first. See who should not use ozone therapy.

When should I get medical help?

Call emergency services for trouble breathing, chest pain, sudden weakness, numbness, vision or speech changes, or a severe headache after a spine or epidural injection. Call your provider for fever, redness, swelling or pus at an injection site, or for symptoms that last more than a few days or get worse with each session.

For the wider picture, including the FDA's position and how ozone therapy safety is argued, see the safety of ozone therapy and the FDA "toxic gas" statement, explained.

Frequently asked questions

What are the most common side effects of ozone therapy?

Mild ones: a short feeling of warmth, a mild headache, pain or a small bruise at the injection site, and for some people tingling lips, nausea or a bad taste during IV ozone. Bloating or constipation can follow rectal insufflation.

Is ozone therapy dangerous?

Serious harm has been reported, but the Madrid Declaration ties it mostly to malpractice: direct IV gas injection, poor sterile technique, and invasive injections by poorly trained operators. Used at the right dose, by the right route, by trained people, it describes ozone as nontoxic.

Can ozone therapy kill you?

Deaths appear in the published case reports. The Declaration lists four from air embolism after direct IV injection of ozone gas, plus a few from infections or complications after spine and disc injections. It says most fatal cases were the result of malpractice. These events are extremely rare compared with the number of treatments given (see "How rare are serious side effects?" above).

Is it normal to have a headache after ozone therapy?

A mild, short headache is listed among the mild (grade 1) side effects. A severe headache after a spine or epidural injection is not, and needs medical care.

Does breathing ozone cause side effects?

Yes. Ozone gas is harmful to the lungs and should never be inhaled. See why you can’t breathe ozone.

Sources

1. ISCO3. Madrid Declaration on Ozone Therapy, 4th edition (ISCO3, 2025). Sections 2.1 to 2.6 and 16. isco3.org
2. Bocci V. Ozone as Janus: this controversial gas can be either toxic or medically useful. Mediators of Inflammation. 2004;13(1):3-11. PMID 15203558.
3. Bocci V. Is it true that ozone is always toxic? The end of a dogma. Toxicol Appl Pharmacol. 2006;216(3):493-504. PMID 16890971.