© 2022 Elsevier Masson SASObjectives: Aims of this study were to demonstrate influence of contraction type on irisin and metabolome, and reveal the unknown relationships of irisin with metabolites and metabolic pathways. Equipment and methods: Sixteen healthy male athletes exercised on a dynamometer for 5 to 6 minutes concentrically and isometrically 3-weeks apart in a sports medicine clinic. Independent variables were body composition parameters, handgrip strength, weekly exercise volume, maximal heart rate achieved during the training, and Borg ratings. Dependent variables were plasma irisin and metabolic profiles. ELISA analysed plasma irisin. Untargeted metabolomic profile was assessed by Q-TOF LC/MS instrument. Selected peaks were uploaded to MetaboAnalyst 5.0 software to identify Kyoto Encyclopedia of Genes and Genomes codes. Results: Concentric but not isometric exercise increased plasma irisin and an average of 23% change was observed in the former intervention (P = 0.007). Leg muscle mass and physical activity level in the week before exercise correlated negatively with irisin fold-change (r = −0.543, P < 0.05; r = −0.481, P = 0.059, respectively). Untargeted metabolomics revealed metabolites correlated with irisin. Concentric exercise activated fatty acid elongation and degradation pathways whereas both types of exercise affected arachidonic acid metabolism, steroid hormone biosynthesis, and regulation of lipolysis in adipocytes pathways. Conclusions: Concentric exercise and isometric exercise differ in metabolic response and irisin stimulation. Recent physical activity status may have an impact on the released irisin in response to exercise. Irisin-related metabolites and pathways that will guide future studies have been revealed by non-targeted metabolomics approach for the first time.