<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>The aim of the present study was to investigate the oxidative–antioxidative systems and effects of different antidepressants on these systems in patients with major depressive disorder (MDD).</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>Ninety‐six patients with a Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM‐IV) diagnosis of MDD and 54 healthy controls were included in the study. Plasma malondialdehyde (MDA) levels and susceptibility of red blood cells (RBCs) to oxidation were determined to investigate the oxidative status, plasma vitamin E, vitamin C, serum total carotenoid levels, total antioxidant capacity (TAOC), RBC superoxide dismutase (SOD) and whole blood glutathione peroxidase (GPx) activities were measured to investigate the antioxidative defence before and after 6 weeks of antidepressant treatment.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Plasma MDA levels and susceptibility of RBCs to oxidation were significantly higher in the MDD group compared with the control group. RBC SOD activity was significantly increased in patients with MDD, and furthermore there was a significant positive correlation between the severity of the disease and SOD activity.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>MDD is accompanied with oxidative stress; however, oxidative–antioxidative systems do not seem to be affected by 6 weeks of antidepressant treatment. Copyright © 2007 John Wiley & Sons, Ltd.</jats:p></jats:sec>