Statins are associated with adverse effects in skeletal muscle. This study tested the hypothesis that atorvastatin would increase the respiratory exchange ratio (RER) at rest and during exercise. Twenty-eight healthy subjects (mean age 52 years) were enrolled in a double-blind, placebo-controlled, randomized study of the effects of atorvastatin (40 mg/day) on whole body energetics over 8 weeks. Ventilatory gas exchange measurements, at rest and during bicycle ergometry, were used to assess muscle oxidative metabolism. Thirteen subjects from each treatment arm completed the study. Eight weeks of atorvastatin lowered plasma low-density lipoprotein cholesterol concentration but had no effect on resting or submaximal energy expenditure, RER, or calculated fatty acid oxidation rates. Atorvastatin did not affect maximal exercise oxygen consumption or the anaerobic threshold. Eight weeks of atorvastatin therapy was not associated with alterations in substrate oxidation, or muscle oxidative function at rest, or during exercise in healthy adults.