Weight loss and hypolipidemic drugs can improve lipid and adipokine levels. We assessed the effects of rimonabant, alone and in combination with fenofibrate or ezetimibe, on adipokine levels in obese/overweight patients with dyslipidemia. Overweight/obese patients (n = 60, body mass index = 27-40 kg/m(2)) with mixed dyslipidemia were recruited. Patients received a hypocaloric diet and were randomized to rimonabant 20 mg/d (group R, n = 20), rimonabant 20 mg/d plus fenofibrate 200 mg/d (group RF, n = 20), or rimonabant 20 mg/d plus ezetimibe 10 mg/d (group RE, n = 20). After 3 months, leptin concentration was significantly reduced in all groups (-38%, P < .005; -40%, P < .005; and -44%, P < .001 in the R, RF, and RE groups, respectively). Total adiponectin remained unaltered. Visfatin concentration decreased significantly only in the RE and RF groups (-18% and -38%, respectively; P < .047). Treatment with rimonabant may improve adipokine levels in overweight/obese patients with dyslipidemia. The addition of fenofibrate or ezetimibe may reinforce this effect.