The results of several recent studies indicated that free radicals are involved in the biochemical mechanisms that underlie neuropsychiatric disorders. In the present study, we evaluated changes in oxidative stress and human 8-hydroxyguanine glycosylase1 gene (hOGG1) expression in depressive patients with acute leukemia. Ninety two cases were assessed using the Zung self-rating depression scale (SDS) and multiple-item questionnaires. We measured total antioxidant capacity (T-AOC) and the concentrations of reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) during a pre-treatment period. The steady-state expression of hOGG1 mRNA transcripts was monitored. The incidence of depression was 47.83%. There was a significant decrease in serum T-AOC and SOD concentrations in depressive patients compared to the control subjects, whereas the opposite was the case for serum concentrations of ROS, NO and MDA. Real-time polymerase chain reaction (PCR) revealed that hOGG1 mRNA expression was greater in depressive patients than in the controls. Person correlation analysis revealed that depression was correlated positively with sex, the course of the disease and hOGG1 mRNA expression; depression was correlated negatively with T-AOC. Based on these results, we conclude that the antioxidant system is impaired in leukemic patients with affective disorders. Therefore, oxidative stress may play an important role in the pathophysiology of depression.