In this prospective study, we investigated the effects of antidepressant therapy on total antioxidant capacity and free radical levels in patients with major depressive disorder (MDD). We recruited thirty-five first-episode patients who met the criteria of the Fourth Edition of Diagnostic and Statistical Manual of Mental Disorders of MDD and 35 age- and sex-matched healthy controls. Superoxide and hydroxyl radicals were measured to investigate oxidative status and the total radical-trapping antioxidant parameter (TRAP) assay was performed to evaluate antioxidant capacity in healthy controls and in patients before and after receiving a 12-week regimen of sertraline. The severity of depression was evaluated using the 17-item Hamilton Depression Rating Scale (HDRS). Before treatment, the mean HDRS score in patients with MDD was 26.11±4.93. Of the 35 patients with MDD, 19 (54.29%) completed the 12-week treatment regimen and all achieved remission. Patients with MDD had significantly lower TRAP baseline values than healthy controls. After adjusting for age, sex, occupation, education and marital status, we found that HDRS score was negatively correlated with TRAP value and level of superoxide radicals. After treatment, the MDD group demonstrated significantly higher TRAP values and significantly lower levels of superoxide and hydroxyl radicals. In conclusion, MDD patients are accompanied by lowered antioxidant capacity than healthy individuals. Antidepressant treatment for 12 weeks results in increased antioxidant capacity and a decrease in circulating free radicals. Key words: major depressive disorder; antidepressant; antioxidant capacity; free radical, total radical-trapping antioxidant parameter (TRAP).