Oxidative stress has been suggested to contribute to the pathophysiology of schizophrenia. Increased oxidative stress is the result of either an increased production of free radicals or a depletion of the endogenous antioxidants. However, whether this imbalance of oxidant-antioxidant status in schizophrenia is integral to disease itself or the effect of antipsychotic drugs is not clearly understood. The present study was undertaken to evaluate the effect of olanzapine and risperidone on oxidative stress, and anti oxidant status. A total of 179 patients were enrolled, and 93 of them completed the study. Malondialdehyde (MDA) and reduced glutathione (GSH) were measured for oxidative stress assessment. Plasma levels of ascorbic acid (vitamin C) and α-tocopherol (vitamin E) were measured for anti-oxidant status evaluation. All patients were studied at baseline, and after 3 months  treatment with olanzapine or risperidone. 30 apparently healthy people were taken as control. The schizophrenia group presented higher levels of oxidative stress than the control group, as revealed by elevated quantities of the pro-oxidant MDA, and decreased levels of the antioxidants GSH, plasma α-tocopherol and ascorbic acid (P< 0.01). After 3 months in both olanzapine and risperidone treated groups MDA levels were reduced significantly (P < 0.01). However, levels of erythrocyte GSH, plasma vitamin E, and vitamin C were increased significantly (P < 0.01). Therefore, atypical antipsychotics like olanzapine and risperidone improved the antioxidant status which might play a role in the improvement of schizophrenia symptoms.