PURPOSE: High-intensity interval training (HIIT) is a potential alternative to traditionally recommended steady state exercise for providing health benefits in adolescents, yet its dose-response relationship in this cohort remains unclear, as does its translatability to real-world, nonclinical settings. The present study adopts a novel dose-response design to investigate the effects of undertaking 8 wk of HIIT on the cardiometabolic health of low-active male adolescents. METHODS: Twenty-six male adolescents (age 16 ± 1 yr), identified as low active by nonparticipation in structured sport and physical education classes, were randomly assigned to one of five treatment groups. Corresponding with their group numbers (1-5), participants completed a number of HIIT "sets," which consisted of 4 repeated bouts of 20-s near-maximal exertion interspersed with 10-s passive recovery. Participants performed two HIIT sessions and one resistance training session each week for 8 wk. Baseline and follow-up health measures consisted of peak oxygen uptake (V˙O2peak) with an incremental ramp test to volitional exhaustion; body composition (including visceral fat mass, body fat, and lean tissue mass) with dual-energy x-ray absorptiometry; and lipid profile, glucose, insulin, and interleukin-6 from blood analysis. All health outcomes were analyzed as percentage changes, and data were modeled using a quadratic function to explore dose-response relationships. RESULTS: Significant improvements were observed for V˙O2peak (∼6%), body fat percentage (∼4%), visceral fat mass (∼10%), and waist circumference-to-height ratio (∼3%), but there was no clear effect of dose across groups. CONCLUSIONS: Low-active adolescent males performing a single HIIT set twice weekly, in addition to one resistance training session, gained meaningful improvements in fitness and body composition. Performing additional HIIT sets provided no additional improvements to those of the lowest dose in this study.