McArdle’s disease (MD) is well known as a metabolic myopathy due to myophosphorylase deficiency. We examined monocarboxylate transporters (MCT) and creatine kinase (CK) protein content in skeletal muscle from 12 patients with MD and 12 age-matched controls, to evaluate potential cellular adaptations to compensate for the loss of glycogenolysis. MD muscle had higher protein content of MCT1 and mitochondrial CK (mt-CK), with no changes in the activities of citrate synthase (CS) and cytochrome c oxidase (COX) and voltage-dependent anion channel (VDAC) protein, as compared to controls. These results suggest that lactate uptake via MCT1 could be important to increase the pyruvate availability, and that mt-CK could be important to maintain phosphocreatine concentration and thus local ATP availability for MD patients, under conditions of reduced energy flux due to inborn errors of metabolism. Collectively, the above data suggest that the proteins related to extra-muscular fuel uptake and intra-muscular energy transduction are up-regulated without change in mitochondrial mass in MD muscle. Additionally, our findings support the effectiveness of carbohydrate for MD patients, and also highlight a potential role for creatine supplementation in the treatment of this population.