Exercise modality differentially alters body composition and physical performance. Metabolic changes underlying these outcomes can be tracked through assessment of circulating metabolites. Here, global responses to an acute bout of aerobic or anaerobic exercise were compared in the serum of male and female subjects using a discovery-based metabolomics platform.On separate days, 40 healthy, active participants completed 45 min of aerobic cycling or resistance exercise, and blood samples were collected at rest, immediately after (T1) and 1 hour post-exercise (T2) to examine the serum metabolomic landscape.The two exercise metabolomes appeared more similar than different in this healthy cohort. Overall, metabolomic signatures of both exercise modalities were markedly altered from rest at T1, and returned toward baseline by T2. Metabolomic perturbations at T1 and the T1-T2 rate of recovery post-exercise were greater following aerobic cycling than resistance exercise. Shared signatures included elevations in purine metabolism, substrate catabolism and mobilization, and inflammatory signaling. Aerobic exercise resulted in greater substrate diversity and use of fatty acids, whereas resistance exercise displayed higher purine turnover and glycolytic flux.Individual metabolite differences between conditions were seen in magnitude but not direction. Metabolomic signatures of the exercise responses appeared fairly robust across exercise modalities. An initial perturbation and subsequent shift toward recovery by an hour post-exercise defined the signature in our healthy cohort. The expedited recovery following aerobic cycling may be explained by globally elevated lipid metabolism.