ImportanceChildhood obesity is a risk factor associated with type 2 diabetes, cardiovascular disease, and mental disorders later in life. Investigation of the parallel effects of a defined exercise program on cardiometabolic and mental health in children with overweight or obesity may provide new insights on the potential benefits of exercise on overall health.ObjectiveTo investigate the effects of a 20-week exercise program on cardiometabolic and mental health in children with overweight or obesity.Design, Setting, and ParticipantsThis secondary analysis of a parallel-group randomized clinical trial was conducted in Granada, Spain, from November 1, 2014, to June 30, 2016. Data analyses were performed between February 1, 2020, and July 14, 2022. Children with overweight or obesity aged 8 to 11 years were eligible, and the study was performed in an out-of-school context.InterventionThe exercise program included 3 to 5 sessions/wk (90 min/session) of aerobic plus resistance training for 20 weeks. The wait-list control group continued with their usual routines.Main Outcomes and MeasuresCardiometabolic outcomes as specified in the trial protocol included body composition (fat mass, fat-free mass, and visceral adipose tissue), physical fitness (cardiorespiratory, speed-agility, and muscular), and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure). Cardiometabolic risk score (z score) was calculated based on age and sex reference values for levels of triglycerides, inverted high-density lipoprotein cholesterol, and glucose, the mean of systolic and diastolic blood pressure, and waist circumference. An additional cardiometabolic risk score also included cardiorespiratory fitness. Mental health outcomes included an array of psychological well-being and ill-being indicators.ResultsThe 92 participants included in the per-protocol analyses (36 girls [39%] and 56 boys [61%]) had a mean (SD) age of 10.0 (1.1) years. The exercise program reduced the cardiometabolic risk score by approximately 0.38 (95% CI, −0.74 to −0.02) SDs; decreased low-density lipoprotein cholesterol level by −7.00 (95% CI, −14.27 to 0.37) mg/dL (to convert to mmol/L, multiply by 0.0259), body mass index (calculated as weight in kilograms divided by height in meters squared) by −0.59 (95% CI, −1.06 to −0.12), fat mass index by −0.67 (95% CI, −1.01 to −0.33), and visceral adipose tissue by −31.44 (95% CI, −58.99 to −3.90) g; and improved cardiorespiratory fitness by 2.75 (95% CI, 0.22-5.28) laps in the exercise group compared with the control group. No effects were observed on mental health outcomes.Conclusions and RelevanceIn this secondary analysis of a randomized clinical trial, an aerobic plus resistance exercise program improved cardiometabolic health in children with overweight or obesity but had no effect on mental health.Trial RegistrationClinicalTrials.gov Identifier: NCT02295072