Purpose: To investigate the effects of a low- versus high-intensity aerobic training on biomarkers of inflammation and endothelial dysfunction in adolescents with obesity. Methods: Sixty-two adolescents with obesity [age = 15 (14) y, body mass index = 34.87 (4.22) kg·m−2] were randomized to receive either a high-intensity training (HIT, n = 31) or a low-intensity training (LIT, n = 31) for 24 weeks. All participants also received nutritional, psychological, and clinical counseling. Leptin, total and subtype leukocyte counts, tumor necrosis factor-alpha, interleukin-6, myeloperoxidase, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were obtained at baseline and after 24 weeks. Results: HIT reduced neutrophils [from 4.4 (1.9) to 3.6 (1.3) µL−1 × 103; P = .01] and monocytes [from 7.2 (2.5) to 5.2 (1.8) µL−1 × 102; P < .01], but LIT increased neutrophils [from 4.5 (1.7) to 5.2 (3.3) µL−1 × 103; P = .01]. Although tumor necrosis factor-alpha increased in LIT [from 13.3 (7.5) to 17.7 (10.8) pg·mL−1; P = .01], it decreased in HIT [from 12.4 (7.5) to 11.3 (6.2) pg·mL−1; P = .01]. No changes in leukocyte counts, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and homeostasis assessment model for insulin resistance were observed. Conclusions: Both HIT and LIT improved the inflammatory profile. The study, however, indicated that the number of biomarkers and the magnitude of changes were higher in the HIT compared with LIT.