STUDY OBJECTIVE: To assess the effects of fenofibrate therapy on concentrations of plasma ubiquinol-10 and ubiquinone-10-the reduced and oxidized forms, respectively, of coenzyme Q(10). DESIGN: Prospective, open-label, non-controlled study. SETTING: University clinic and laboratory. PATIENTS: Eighteen patients with hyperlipidemia and type 2 diabetes mellitus. INTERVENTION: Patients received fenofibrate 150 mg/day for 12 weeks. MEASUREMENTS AND MAIN RESULTS: Metabolic parameters were assessed 4, 8, and 12 weeks after the start of fenofibrate treatment. Plasma ubiquinol-10 and ubiquinone-10 levels were measured by reverse-phase high-performance liquid chromatography. At 4, 8, and 12 weeks, significant reductions in fasting triglyceride levels and significant increases in high-density lipoprotein cholesterol levels were noted. Total cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and adiponectin levels, however, did not change significantly. Plasma ubiquinol-10 concentrations significantly increased after 8 and 12 weeks (p<0.05 for both), whereas ubiquinone-10 concentrations tended to decrease, especially at 12 weeks. CONCLUSION: Our findings suggest that fenofibrate may help produce energy or prevent oxidation by increasing plasma ubiquinol-10 concentration; this effect may protect against the development and progression of atherosclerosis. In addition, treatment with fenofibrate demonstrated a favorable effect on serum lipid parameters.