The aim of the present study was to evaluate in patients with acute lymphoblastic leukemia (ALL), the oxidative status and antioxidant defense and its involvement in the relapse of ALL. The plasmatic levels of malondialdehyde, advanced oxidation of protein products and reduced glutathione (GSH), and the plasmatic activities of catalase, superoxide dismutase (SOD), and glutathione peroxidase were determined in 34 patients who were newly diagnosed with ALL and compared with 92 healthy individuals. The plasmatic concentrations of malondialdehyde and advanced oxidation of protein products were higher in ALL patients than in controls and increased during chemotherapy. A decrease in glutathione peroxidase activity and an increase in catalase and SOD activities and GSH plasma levels were observed in ALL patients, as compared with sex-matched controls. Moreover, SOD activity and GSH levels were significantly correlated with the relapse of ALL patients. These data suggest the involvement of oxidative stress in acute lymphoid leukemias and leukemic relapse.