The present study aimed to determine whether any gender-related difference exists concerning oxidative stress parameters in a population of 231 subjects, and if these changes might be related to gender-associated differences in major depressive disorder (MDD) or bipolar disorder (BD) vulnerability. This is a case-control nested in a population-based study. The initial psychopathology screen was performed with the Mini-International Neuropsychiatric Interview and the diagnostic was further confirmed with the Structured Clinical Interview for DSM-IV. Blood samples were obtained after the interview and the oxidative stress parameters such as uric acid, advanced oxidation protein product (PCC) and lipid hydroperoxides (TBARS) were determined. Our results indicated a higher prevalence of MDD and BD in women when compared to men. In addition, significant gender differences were found in the levels of PCC (0.27 ± 0.27 vs. 0.40 ± 0.31 nmol CO/mg protein, men vs. women, respectively; P = 0.02) and uric acid (4.88 ± 1.39 mg/dL vs. 3.53 ± 1.02 mg/dL, men vs. women, respectively; P = 0.0001), but not in TBARS (0.013 ± 0.01 nmol/mg of protein vs. 0.017 ± 0.02 nmol/mg of protein, men vs. women respectively; P = 0.243). After sample stratification by gender, no association was found between oxidative stress parameters and clinical diagnosis of MDD and BD for women (P = 0.516 for PCC; P = 0.620 for TBARS P = 0.727 for uric acid) and men (P = 0.367 for PCC; P = 0.372 for TBARS P = 0.664 for uric acid). In this study, women seem more susceptible to oxidative stress than male. However, these gender-based differences do not seem to provide a biochemical basis for the epidemiologic differences in mood disorders susceptibility between sexes.