Background: Intense physical exercise leads to inflammation, oxidative stress and muscle damage, and these responses are of greater magnitude in people with obesity. Melatonin (MLT) is considered an endogenous antioxidant which may have beneficial effects against inflammation, oxidative stress and promote tissue repair after exercise. The aim of this study was to examine the effect of MLT on inflammatory parameters, oxidative stress and muscle damage in people with overweight/obesity after a high-intensity interval exercise (HIIE). Methods: A total of 23 subjects with obesity (9 men and 14 women) age: 33.26 +- 9.81 years, BMI: 37.75 +- 8.87 kg.m2 were randomized to participate in two experimental sessions: HIIE ţ Placebo and HIIE ţ MLT (3 mg). The HIIE protocol corresponds to 8 intervals of 1 min (90% of the maximal aerobic power (MAP)) alternating with 2 min recovery (45% of the MAP). Blood samples were drawn before and 5 min after each exercise session. Results: MLT ingestion attenuated the increase of inflammation (C-reactive protein, white blood cells (P < 0.001, hp2 5 0.45; for both) and Neutrophils (P < 0.01, hp2 5 0.36)) and hepatic and muscle damage (Aspartate aminotransferase (P < 0.01, hp2 5 0.25), Alanine aminotransferase (P < 0.01, hp2 5 0.27) and Creatine kinase (P 5 0.02, hp2 5 0.23). MLT also attenuated the exercise induced lipid and protein peroxidation (i.e., Malondialdehyde (P 5 0.03, hp2 5 0.19) and AOPP (P < 0.001, hp2 5 0.55)). Concerning the antioxidant status, MLT intake increased Thiol (P < 0.01, hp2 5 0.26) and Catalase (P < 0.01, hp2 5 0.32) and decreased Uric acid (P 5 0.02, hp2 5 0.2) and Total bilirubin (P < 0.01, hp2 5 0.33). Conclusions: MLT intake before HIIE reduced muscle damage by modulating oxidative stress and preventing overexpression of the pro-inflammatory mediators in people with obesity.  Kulcsszavak: melatonin, obesity, strenuous exercise, inflammation, oxidative stress