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Fibromyalgia is a chronic disorder with a very complex symptomatology. There is evidence that oxidative stress is increased in fibromyalgia, although it is not known whether this increase is involved as a causative factor in the development of the disease, or whether it is secondary to the patients’ unfit condition. Ozone therapy is thought to act by exerting a mild, transient, and controlled oxidative stress that promotes an up regulation of the antioxidant system and a modulation of the immune system. The objective of the present study was to get a preliminary evaluation of the potential effectiveness of ozone therapy in the management of fibromyalgia. At our knowledge, this is the largest study of patients with fibromyalgia treated with ozone therapy reported in the literature and it demonstrates that the ozone therapy is an effective treatment for fibromyalgia patients without significant side effects.