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Background: The need for energy in strenuous exercises necessitates increased oxygen consumption and hence increased production of reactive oxygen species. It seems that vitamins C and E supplementation reduces exercise-induced oxidative stress. Therefore, this study aimed to investigate the effects of vitamins C and E supplementation on muscle damage and oxidative stress in female athletes. Methods: This four-week randomized, double-blind clinical trial, recruited 64 trained female athletes from gyms in Isfahan, Iran. The subjects were randomly assigned to groups A-D and received vitamin C (250 mg/day), vitamin E (400 international units), both vitamins C and E, and placebo. Blood samples were obtained before and after the intervention to measure muscle damage indices, i.e. aspartate transaminase, creatine kinase, and lactate dehydrogenase, and malondialdehyde. Findings: Among muscle damage indices, only creatine kinase levels significantly reduced between groups at the end of the study (P = 0.030). Considering within group differences, creatine kinase significantly decreased in group A (P = 0.002). No within or between group differences were observed in aspartate aminotransferase levels. Lactate dehydrogenase levels were significantly decreased in group B (P = 0.020). Significant reductions in malondialdehyde levels were also detected in groups A, C and D (P < 0.050). Conclusion: According to our findings, vitamins C and E supplementation can be beneficial in reducing muscle damage indices during aerobic exercises. [ABSTRACT FROM AUTHOR]