Recent data have shown that individuals with low insulin sensitivity (S_i) also have reduced whole-body maximal oxygen uptake. The objectives of this study were to determine, 1) if muscle mitochondrial function was independently related to S_i after adjusting for known determinants of Si; and 2) if lower S_i among African-American (AA) vs. Caucasian-American (CA) women was due to lower muscle mitochondrial function among AA women. Subjects were 37 CA and 22 AA premenopausal women (age: 33.6±6.3 y). Mitochondrial function (time constant of ADP; ADP_tc) was assessed during a 90 s unilateral, isometric contraction using ³¹P-MRS; S_i with an intravenous glucose tolerance test; body composition by DXA; and visceral adipose tissue (VAT) with computed tomography. ANOVA was used to compare AA and CA groups, and multiple linear regression modeling was used to identify independent predictors of S_i. Between-race comparisons indicated that muscle oxidative capacity was lower among AA vs. CA (ADP_tc: 25.6±9.8 vs. 21.4±9.9 s). Multiple linear regression models for the dependent variable S_i contained, 1) VAT and race, and 2) VAT, race, and ADP_tc. Significant independent effects for all predictor variables were observed in both the first (R²=0.345) and second (R²=0.410) models. The partial correlation for race was lower in the second model (-0.404 vs. -0.300) suggesting that muscle mitochondrial function contributed to the racial difference in S_i. Lower muscle mitochondrial function among AA may in part explain lower S_i among AA.