Curcumin may improve blood glucose management, but the mechanism is not fully established. We demonstrated that curcumin (40 mu M) reduced the mitochondrial coupling efficiency (percentage of oxygen consumption coupled to ATP synthesis) of intact skeletal muscle cells. A 30-minute pretreatment with curcumin reduced mitochondrial coupling efficiency by 17.0 +/- 0.4% relative to vehicle (p < 0.008). Curcumin pretreatment also decreased the rate of hydrogen peroxide emission by 43 +/- 13% compared to vehicle (p < 0.05). Analysis of cell respiration in the presence of curcumin revealed a 40 +/- 4% increase in the rate of oxygen consumption upon curcumin administration (p < 0.05 compared to vehicle). No difference in mitochondrial coupling efficiency was observed between vehicle- and curcumin-pretreated cells after permeabilization of cell membranes (p > 0.7). The interaction between curcumin and ursolic acid, another natural compound that may improve blood glucose management, was also examined. Pretreatment with ursolic acid (0.12 mu M) increased the mitochondrial coupling efficiency of intact cells by 4.1 +/- 1.1% relative to vehicle (p < 0.008) and attenuated the effect of curcumin when the two compounds were used in combination. The observed changes to mitochondrial coupling efficiency and hydrogen peroxide emission were consistent with the established effects of curcumin on blood glucose control. Our findings also show that changes to mitochondrial coupling efficiency after curcumin pretreatment may go undetected unless cells are assessed in the intact condition. (C) 2017 Elsevier Inc. All rights reserved.