Energy deficit has shaped human evolution and represents a potent physiological stressor associated with improvements in lifespan and health span in several species. Preserving locomotive capacity has likely been essential for food procurement and survival from starvation during the hunter-gatherer period. However, we have a very limited understanding of the effect of an energy deficit on skeletal muscle, a key tissue for locomotion and metabolic health. Our label-free proteomic analysis discovered that energy deficit shifts skeletal muscle towards an oxidative phenotype as compared to energy balance. This dataset includes targeted proteomic analysis of PLIN2 and PLIN5 peptides using parallel reaction monitoring (PRM) to verify findings from our label-free discovery proteomics data. ClinicalTrials.gov ID: NCT05203133