Objective: To determine whether statin medication in individuals with obesity, dyslipidemia, and metabolic syndrome affects their capacity to mobilize and oxidize fat during exercise. Methods: Twelve individuals with metabolic syndrome pedaled during 75 min at 54 ± 13% ${\dot{\mathrm{V}}\mathrm{O}}_2\text{max}$ (5.7 ± 0.5 metabolic equivalents) while taking statins (STATs) or after 96-hr statin withdrawal (PLAC) in a randomized double-blind fashion. Results: At rest, PLAC increased low-density lipoprotein cholesterol (i.e., STAT 2.55 ± 0.96 vs. PLAC 3.16 ± 0.76 mmol/L; p = .004) and total cholesterol blood levels (i.e., STAT 4.39 ± 1.16 vs. PLAC 4.98 ± 0.97 mmol/L; p = .008). At rest, fat oxidation (0.99 ± 0.34 vs. 0.76 ± 0.37 μmol·kg⁻¹·min⁻¹ for STAT vs. PLAC; p = .068) and the rates of plasma appearance of glucose and glycerol (i.e., Ra glucose–glycerol) were not affected by PLAC. After 70 min of exercise, fat oxidation was similar between trials (2.94 ± 1.56 vs. 3.06 ± 1.94 μmol·kg⁻¹·min⁻¹, STA vs. PLAC; p = .875). PLAC did not alter the rates of disappearance of glucose in plasma during exercise (i.e., 23.9 ± 6.9 vs. 24.5 ± 8.2 μmol·kg⁻¹·min⁻¹ for STAT vs. PLAC; p = .611) or the rate of plasma appearance of glycerol (i.e., 8.5 ± 1.9 vs. 7.9 ± 1.8 μmol·kg⁻¹·min⁻¹ for STAT vs. PLAC; p = .262). Conclusions: In patients with obesity, dyslipidemia, and metabolic syndrome, statins do not compromise their ability to mobilize and oxidize fat at rest or during prolonged, moderately intense exercise (i.e., equivalent to brisk walking). In these patients, the combination of statins and exercise could help to better manage their dyslipidemia.