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High-throughput profiling of metabolic status (metabolomics) allows for the assessment of small-molecule metabolites that may participate in exercise-induced biochemical pathways and corresponding cardiometabolic risk modification. We sought to describe the changes in a diverse set of plasma metabolite profiles in patients undergoing chronic exercise training and assess the relationship between metabolites and cardiometabolic response to exercise.A secondary analysis was performed in 216 middle-age abdominally obese men and women (mean ± SD, 52.4 ± 8.0 yr) randomized into one of four groups varying in exercise amount and intensity for 6-month duration: high amount high intensity, high amount low intensity, low amount low intensity, and control. One hundred forty-seven metabolites were profiled by liquid chromatography-tandem mass spectrometry.No significant differences in metabolite changes between specific exercise groups were observed; therefore, subsequent analyses were collapsed across exercise groups. There were no significant differences in metabolite changes between the exercise and control groups after 24 wk at a Bonferroni-adjusted statistical significance (P < 3.0 × 10−4). Seven metabolites changed in the exercise group compared with the control group at P < 0.05. Changes in several metabolites from distinct metabolic pathways were associated with change in cardiometabolic risk traits, and three baseline metabolite levels predicted changes in cardiometabolic risk traits.Metabolomic profiling revealed no significant plasma metabolite changes between exercise and control after 24 wk at Bonferroni significance. However, we identified circulating biomarkers that were predictive or reflective of improvements in cardiometabolic traits in the exercise group.