ObjectivesTo investigate the effects of exercise on intelligence, executive functions, academic performance and brain outcomes in children with overweight/obesity. In secondary analyses, we explored potential mediators and moderators of the exercise effects.MethodsA total of 109 children (8-11.9y) with overweight/obesity were randomized (intention-to-treat) and 90 (82.6%) completed the post-exercise evaluation and attended ≥70% of the exercise sessions (per-protocol). Participants in the control group continued with their usual routines and received lifestyle recommendations, whereas the exercise group attended 3 sessions/week of aerobic plus resistance training during 20 weeks. Intelligence, executive functions (cognitive flexibility, inhibition, working memory) and academic performance were assessed with standardized tests; and hippocampal volume with magnetic resonance imaging (MRI).ResultsIn per-protocol analyses, the exercise intervention improved intelligence and cognitive flexibility (medium-large effect sizes observed, 0.4-0.7 SDs). These main effects were consistent in intention-to-treat analyses and after multiple-testing correction. Moreover, we found a positive, small-magnitude (i.e., 0.2-0.3 SDs) effect of exercise on academic performance (total, mathematics and problem solving), which was partially mediated by cognitive flexibility. Inhibition, working memory, hippocampal volume, and other brain MRI outcomes studied were not affected by our exercise program. Our intervention increased cardiorespiratory fitness performance (0.4 SDs) and these changes in fitness mediated some of the effects. Effects were mostly consistent across the studied moderators, except for larger improvements for intelligence in boys compared to girls.ConclusionExercise positively impacts intelligence and cognitive flexibility during development in children with overweight/obesity, without changes in the structural and functional brain outcomes studied.Trial RegistrationClinicalTrials.gov Identifier: NCT02295072SUMMARY BOXWhat is already known on this topic-Pediatric obesity is associated not only with poorer physical health but also with poorer cognitive and brain development.-Previous exercise interventions have mostly focused on executive functions and other dimensions of cognition, yet is largely unknown the extent to which exercise can improve intelligence during childhood, and actually, at any period of life.-Studies integrating effects of exercise on behavioral and brain magnetic resonance outcomes in a single article are scarce.-A in-depth study of the exercise characteristics (mode) and intensity, potential compensatory/contamination effects and role of potential mediators and moderators of the exercise effects is warranted.What this study adds-A 20-week randomized controlled trial of exercise improved intelligence and cognitive flexibility in preadolescent children with overweight/obesity.-Moreover, we found a positive, small-magnitude effect of exercise on academic performance, which was partially mediated by cognitive flexibility.-Cardiorespiratory peak performance mediated some yet not all the exercise effects observed.-The structural and functional brain outcomes studied were not affected by participation in the exercise program.How this study might affect research, practice or policyOur investigation suggests that exercise can positively impact intelligence and cognitive flexibility during a sensitive period of brain development in childhood. This stimulus can positively affect academic performance, as shown in our study, indicating that an active lifestyle during preadolescent development may lead to more successful life trajectories. This is particularly important in children with overweight/obesity who are known to be at higher risk of poorer physical and brain health.