Aim: To determine the safety of Coenzyme Q10 (CoQ10) in breast cancer patients receiving doxorubicin treatment. Methods: Phase I randomized, placebo-controlled, cross-over, dose-finding pharmacokinetic study among women with stage I-III breast cancer receiving 4 cycles of doxorubicin plus cyclophosphamide. The study was designed to test the maximum tolerated dose of CoQ10 using up to 1200 mg/day. Eligible patients were randomized to Arm A (CoQ10 after Cycle 3, followed by placebo after Cycle 4) or Arm B (placebo after cycle 3, followed by CoQ10 after cycle 4). CoQ10 concentrations and total antioxidant capacity (TAC) were measured before and after chemotherapy cycles. Non-compartmental pharmacokinetic parameters of doxorubicin and its active metabolites were measured with and without CoQ10. Paired t-tests assessed intra-patient differences in pharmacokinetic parameters, serum CoQ10 concentrations, TAC and adverse events. Results: Six patients received 300 mg/day of CoQ10 [Arm A (n=3), Arm B (n=3)]. One patient received 600 mg/day of CoQ10 but was discontinued due to non-adherence. Serum CoQ10 concentrations were increased in patients receiving 300 mg/day (mean±SD change: CoQ10, 1.6±0.9 ug/mL; placebo, -0.01±0.3 ug/mL; P=0.01). There were no clinically significant pharmacokinetic interactions between 300 mg/day CoQ10 and doxorubicin and no differences in TAC or adverse events during treatment and nontreatment periods. The trial was closed early due to slow accrual. Conclusions: 300 mg/day of CoQ10 with doxorubicin did not change doxorubicin pharmacokinetics and was not associated with treatment-related adverse events. Future studies should evaluate the long-term effects of CoQ10 at 300 mg/day and safety studies should examine higher doses.