Abstract INTRODUCTION: The role of obesity in diabetes mellitus, hyperlipidemia, colon cancer, sudden death and other cardiovascular diseases has been confirmed by many studies. In this study, it was hypothesized that obesity is an independent risk factor for lipid peroxidation and decreased activity of cytoprotective enzymes in humans. methods: To test the study hypothesis, we assessed lipid peroxidation by measuring the concentrations of plasma malondialdehyde (MDA) and the activity of erythrocyte copper-zinc superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT) in 25 obese women (BMI=30-40 Kg/m2) and 25 women with healthy BMI (19-25Kg/m2). results: The concentration of plasma MDA was significantly higher (P<0.001) in obese women (3.4± 0.7 µmol/L) compared to women with healthy BMI (1.4± 0.3 µmol/L). Furthermore, there was a significantly positive correlation (r =0.75, P<0.0001) between BMI and plasma MDA. On the other hand, women with healthy BMI had significantly higher (P<0.001) erythrocyte CuZn-SOD (873± 52 U/g Hb) and GPX (64.7± 14.2 U/g Hb) activity than obese women (660± 39 U/g Hb) and (48.5± 13.1 U/g Hb), respectively. Furthermore, erythrocyte CuZn-SOD and GPX activity were negatively correlated with BMI (r =-0.52, P<0.0001 and r =-0.42, P<0.001), respectively. No significant difference was observed between two groups in erythrocyte CAT activity. CONCLUSIONS: From these observations, it is concluded that obesity even in the absence of smoking, diabetes, renal or liver disease can decrease the activities of body’s protective antioxidants, and can enhance the systemic oxidative stress. Keywords: Obesity, Lipid peroxidation, Cytoprotective enzymes, Oxidative stress, Women.