Sex differences in energy metabolism during acute, sub-maximal exercise are well documented. Whether these sex differences influence metabolic and physiologic responses to sustained, physically demanding activities is not well characterized. This study aimed to identify sex differences within changes in the serum metabolome in relation to changes in body composition, physical performance, and circulating markers of endocrine and metabolic status during a 17-day military training exercise. Blood was collected, and body composition and lower-body power measured before and after training on 72 cadets (18 women). Total daily energy expenditure (TDEE) was assessed using doubly labeled water in a subset. TDEE was greater in men (4,085±482kcal/d) than women (2,982±472kcal/d, p<0.001), but not after adjustment for dry lean mass (DLM). Men tended to lose more DLM than women (-0.2[-0.3,-0.1] vs. -0.0[-0.0,0.0] kg, p=0.063, Cohen's d=0.50) and have greater reductions in lower body power (-244[-314,-174] vs. -130[-209,-51] Watts, p=0.085, d=0.49). Reductions in DLM and lower body power were correlated ( r=0.325, p=0.006). Women demonstrated greater fat oxidation than men (Δfat mass/DLM: -0.20[-0.24,-0.17] vs. -0.15[-0.17,-0.13] kg, p=0.012, d=0.64). Metabolites within pathways of fatty acid, endocannabinoid, lysophospholipid, phosphatidylcholine, phosphatidylethanolamine, and plasmalogen metabolism increased in women relative to men. Independent of sex, changes in metabolites related to lipid metabolism were inversely associated with changes in body mass and positively associated with changes in endocrine and metabolic status. These data suggest that during sustained military training, women preferentially mobilize fat stores compared with men, which may be beneficial for mitigating loss of lean mass and lower body power.