Introduction: Antioxidants prevent the progression of neuropsychiatric disorders, such as bipolar disorder (BD). Omega-3 fatty acid supplementation helps prevent lipid peroxidation and improve antioxidant status. This study aims to investigate the effect of omega-3 supplementation on serum levels of antioxidant status in patients with BD. 
Methods: In this study, 28 patients with BD received an omega-3 fatty acid supplement (2 g/daily) while the other 28 patients received edible paraffin oil (2 g/daily) for 60 days. The activities of superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC) were evaluated in pre-intervention and post-intervention. 
Results: The results showed that omega-3 supplementation increased the activities of SOD (12.94±3.84 U/mL vs 17.72±3.59 U/mL) and CAT (5.08±1.61 nmol/min/mL vs 6.43±1.33 nmol/min/mL) in post-intervention compared to pre-intervention (P=0.001). The results also showed that omega-3 supplementation increased the activities of SOD (17.72±3.59 U/mL vs 13.79±3.12 U/mL) and CAT (6.43±1.33 nmol/min/mL vs 4.89±1.45 nmol/min/mL) compared to the control group in post-intervention (P=0.001). Omega-3 supplementation did not have significant effects on the serum concentration of TAC compared to pre-intervention (P=0.373) and control group (P=0.604). 
Conclusion: Omega-3 supplementation increased the activities of SOD and CAT and may decrease the progression of disease via increasing antioxidant status.