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Bipolar disorder (BPD) is a chronic and recurrent mood disorder characterized by episodes of mania, hypomania, and major depression. Based on available evidence, mitochondrial dysfunction, oxidative stress, and inflammation have important roles in the pathophysiology of bipolar depression. More specifically, it seems that coenzyme Q10 (CoQ10), a mitochondrial modulator, as well as an antioxidant and anti-inflammatory agent, might be effective in modulating these pathophysiological pathways. Accordingly, the aim of this study was to investigate whether and to what extent, compared with placebo, adjuvant CoQ10 might improve symptoms of depression in patients with BPD.A total of 69 patients with BPD with a current depressive episode were randomly assigned either to the adjuvant CoQ10 (200 mg/d) or to the placebo group. Standard medication consisting of mood stabilizers and antidepressants was consistent 2 months prior and during the study. Depression severity for each patient was assessed based on the Montgomery-Asberg Depression Rating Scale scores at baseline, fourth week, and eighth week of the study.Symptoms of depression decreased over time in both groups. Compared with the placebo group, adjuvant CoQ10 to a standard medication improved symptoms of depression after 8 weeks of treatment. In addition, at the end of the study, it turned out that more responders were observed in the CoQ10 group, compared with the placebo group. CoQ10 had minimal adverse effects and was well tolerated.The present pattern of results suggests that among patients with BPD, compared with placebo, adjuvant CoQ10 probably because of its antioxidant and anti-inflammatory properties can improve symptoms of depression over a period of 8 weeks.