Oxidant nitric oxide (NO) and antioxidant superoxide dismutase (SOD) have been implicated to play a role in the pathogenesis of bipolar disorders. This is the first prospective study aimed to evaluate NO levels and SOD activity in bipolar disorder (type I manic episode) (BD-ME). 29 inpatient subjects with BD-ME and 30 healthy controls were included. Serum NO levels and SOD activity have been studied at 1st (NO [1st] and SOD [1st] respectively) and 30th days (NO [30th] and SOD [30th] respectively) after treatment. The clinical outcome was measured by Bech-Rafaelson Mania Scale (BRMS). The mean NO [1st] (p <.001) and NO [30th] levels (p <.00 1) were higher than controls, but SOD [ I st] (p <.001) and SOD [30th] (p <.001) activities in BD-ME were lower than controls. SOD1 activity was higher than SOD [30th] (p <.001), while there was no significance in comparison between NO [1st] and NO [30th] (p <.05).