Background and aims: Studies have already pointed out a possible pathophysiological role of oxidative and antioxidative molecules in bipolar disorder. We aimed to evaluate the activity and levels of antioxidant superoxide dismutase (SOD), and oxidant nitric oxide (NO), in bipolar I depressive episode (BD-DE) patients in a prospective design. Method: 30 BD-DE patients, diagnosed according to DSM IV, and 30 healthy volunteer controls were included. The serum levels of NO and SOD have been studied when admitted to hospital (1st) and on the 30th days. Clinical outcome was measured by Hamilton Depression Scale (HAM-D). The patients were allowed to have their treatments. One patient was dropped out due to insufficient sampling. Results: As in the previous studies, NO 1st day levels were significantly higher in patients and SOD 1st day activity was significantly low (p < 0.0 1). NO levels significantly decreased (p < 0.0 1) and normalized, as SOD activity significantly increased but did not reach to the controls' levels (p < 0.01) on the 30th day. Conclusion: Despite normalized NO levels, persistent low SOD activity might point out an oxidative imbalance in BD-DE. Chronic low SOD activity may be associated with incapacity of coping with oxidative stress. This research connotes the probable oxidative imbalance in BD-DE and discusses that phenomenon within the continuum of the disease state. (C) 2007 Elsevier B.V. All rights reserved.