Heat-stressed pigs experience metabolic alterations, including altered insulin profiles, reduced lipid mobilization, and compromised intestinal integrity. This is bioenergetically distinct from thermal neutral pigs on a similar nutritional plane. To delineate differences in substrate preferences between direct and indirect (via reduced feed intake) heat stress effects, skeletal muscle fuel metabolism was assessed. Pigs (35.3 ± 0.8 kg) were randomly assigned to three treatments: thermal neutral fed ad libitum (TN, 21°C, n=8), heat stress fed ad libitum (HS, 35°C, n=8), and TN, pair-fed to HS intake (PF, n=8) for 7 days. Body temperature (TB) and feed intake (FI) were recorded daily. Longissimus dorsi muscle was biopsied for metabolic assays on days -2, 3, and 7 relative to initiation of environmental treatments. Heat stress increased TB and decreased FI (P < 0.05). Heat stress inhibited incomplete fatty acid oxidation (P < 0.05) and did not alter glucose oxidation. Metabolic flexibility decreased in HS pigs compared to TN and PF controls (P < 0.05). Both phosphofructokinase and pyruvate dehydrogenase (PDH) activities increased in PF (P < 0.05), however, TN and HS did not differ. Heat stress inhibited citrate synthase and beta hydroxyacyl-CoA dehydrogenase (βHAD) activities (P < 0.05). Heat stress did not alter PDH phosphorylation or carnitine palmitoyltransferase 1 abundance, but reduced acetyl-CoA carboxylase 1(ACC1) protein abundance (P < 0.05). In conclusion, HS decreased skeletal muscle fatty acid oxidation and metabolic flexibility, likely involving βHAD and ACC regulation.