Efficacy of Oxygen–Ozone Therapy for Shoulder Disorders: A Systematic Review of Randomized Controlled Trials

Background: Shoulder disorders are among the leading causes of musculoskeletal pain and disability worldwide. Despite the widespread use of corticosteroid injections, concerns regarding their short-term efficacy and potential adverse effects have encouraged research into alternative therapies such as oxygen–ozone therapy. This systematic review aimed to evaluate the efficacy of oxygen–ozone therapy in the management of shoulder disorders. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted up to 16 March 2026, according to PRISMA guidelines. Randomized controlled trials investigating localized oxygen–ozone injections for shoulder disorders were included. Pain scores and shoulder function were the main outcomes considered. Study quality was assessed using the Cochrane Risk of Bias 2 tool. Results: Five randomized controlled trials involving 263 participants with shoulder impingement syndrome, adhesive capsulitis, or chronic rotator cuff syndrome were included. Given the heterogeneity of the included studies, we only performed a qualitative synthesis. Oxygen–ozone therapy demonstrated significant improvement in pain and shoulder function across all of the included studies. Corticosteroid injections generally showed superior short-term pain relief, whereas oxygen–ozone therapy demonstrated more persistent clinical improvements during medium-to-long follow-up periods. Studies employing multiple ozone injection protocols reported more stable outcomes when compared with single-injection approaches. No major adverse events related to oxygen–ozone therapy were reported. However, substantial heterogeneity was observed regarding injection protocols, ozone concentrations, number of injections, and follow-up duration. Conclusions: Oxygen–ozone therapy appeared to be a potentially effective treatment option for shoulder disorders, particularly in patients with contraindications to corticosteroids or chronic degenerative conditions. While corticosteroid injection might provide short-term symptom relief, repeated oxygen–ozone injection protocols seemed to offer sustained clinical benefits over time. Further high-quality randomized controlled trials with standardized protocols and longer follow-ups are needed to better define the role of oxygen–ozone therapy in shoulder rehabilitation.