Lipedema is a disease characterized by enlargement of the subcutaneous tissue and is observed only in the female population. Recently, the inflammatory cascade has been suggested to be the initiator of lipoedema and to play a role in its progression. The presence of pain in the involved areas is the most important symptom affecting the patient's QoL. In the literature, ozone therapy is used both locally and systemically in many diseases in which inflammation is involved in the etiopathogenesis. There are many studies on plantar fasciitis, lateral epicondylitis, rheumatoid arthritis, osteoarthritis, etc. In addition to its anti-inflammatory properties, ozone therapy, which has analgesic and aseptic properties, has not been found in the literature in patients with lipedema. The aim of this study was to investigate the effect of ozone therapy on pain symptoms and subcutaneous tissue thickness in patients with lipedema and to compare local and systemic ozone applications in these patients.