Previous studies have demonstrated decreases in whole-body and muscle fat oxidation in obese individuals. Because muscle also uses ketone bodies, and because the ketone body oxidation pathway differs from that of fatty acid oxidation, this study was initiated to determine whether there were differences in ketone body metabolism between obese and lean subjects. Plasma β-hydroxy-butyrate (β-OHB) concentration was measured in 47 lean and 47 age-matched obese women, and the rate of β-OHB oxidation by muscle homogenates was measured in a subset of 8 lean and 8 obese women. Plasma free fatty acid levels, which have been reported to correlate with ketone body production, were higher (P < .05) in the obese than in the lean women (662 ± 46 and 463 ± 44 nmol/L, respectively) as was plasma insulin level. However, the β-OHB concentration was lower in obese than in lean subjects (235 ± 17 and 323 ± 29 μmol/L, respectively; P < .05). The rate of β-OHB oxidation was also lower (P < .05) in muscle of the obese than that of the lean group (139.6 ± 12.6 vs 254.6 ± 30.0 nmol of CO₂ produced per gram of tissue per hour). These data illustrate that production and use of ketone bodies are lower in obese women than in lean controls. The decreased oxidation of ketone bodies by muscle is consistent with aberrations in muscle metabolism in the obese individuals that most likely relates to a decrease in mitochondrial numbers.