Bipolar disorder (BPD) is a severe and chronic mental disease with high rates of social and functional disability. To explain the emergence and maintenance of BPD, increasing attention has been focused on dimensions of inflammation and oxidative stress (OTS). Coenzyme Q10 (CoQ10) is known for its anti-oxidant and anti-inflammatory effects; accordingly, the aim of the present study was to investigate, if compared to placebo, adjuvant CoQ10 might favorably impact on serum levels of inflammatory and OTS biomarkers in patients with BPD during their depressive phase. A total of 89 BPD patients, currently in a depressive episode were allocated by block randomization either to the adjuvant CoQ10 (200 mg/day) condition or to the placebo condition. At baseline and 8 weeks later at the end of the study, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interlukin-6 (IL-6), and IL-10 were assessed. 69 patients completed the 8-week lasting study. Compared to baseline and to the placebo condition, serum levels of TTG and TAC significantly increased, and TNF-α, IL-10, and NO statistically decreased over time in the adjuvant CoQ10 condition. No statistically significant changes were observed for CAT, MDA, and IL-6. The pattern of results suggests that compared to placebo and over a time lapse of 8 weeks, adjuvant CoQ10 favorably impacted on OTS and inflammatory biomarkers in patients with BPD during the depressive episode. Thus, CoQ10 might be considered a safe and effective strategy for treatment of patients with BPD during their depressive phase.