Background: Ischemic stroke is one of the leading causes of death and adult disability. The incidence of ischemic stroke continues to rise in young adults. This study aimed to provide a comprehensive evaluation of metabolic changes and explore possible mechanisms in young ischemic stroke patients without common risk factors. Methods: This study investigated serum metabolomics in 50 young patients with newly suffered ischemic stroke and 50 age-, sex-, and body mass indexâmatched healthy controls. The metabolomic data were analyzed by performing a multivariate statistical analysis.Results: The 197 metabolites, including amino acids, bile acids, free fatty acids, and lipids, were identified in all participants. Multivariate models showed significant differences in serum metabolomic patterns between young patients with ischemic stroke and healthy controls. The stroke patients had increased L-methionine, homocysteine, glutamine, uric acid, GCDCA, and PE (18:0/20:4, 16:0/22:5), and decreased levels of L-citrulline, taurine, PC (16:2/22:6, 16:2/20:5, 15:0/18:2), and SM (d18:1/23:0, d20:0/19:1, d18:1/22:0, d16:0/26:1, d16:0/18:0, d16:0/22:1, d18:1/19:1, d16:0/17:1, d16:1/24:1, d18:1/19:0). Based on the identified metabolites, the metabolic pathways of arginine biosynthesis, glycerophospholipid metabolism, and taurine and hypotaurine metabolism were significantly enriched in the young patients with ischemic stroke. Conclusions: Serum metabolomic patterns were significantly different between young patients with ischemic stroke and healthy controls.