Aim: to verify the effect of a physical education program at school on physical fitness and mental health in children and to determine the individual prevalence of responders. Methods: This is a quasi-experimental study, developed with 67 children aged between 6 and 11 years old. (8.09 ± 1.81). A 21-week intervention was performed, that intervention condition (IC) consisted of sports and circuit training, and nutritional education. For the control condition (CC) classes followed to the Common Curricular National Base. The following variables were evaluated at baseline and post-intervention: physical fitness and mental health through the strength and difficulties questionnaire. Mixed analysis of variance and the prevalence of responders were used for statistical analysis. Results: The main results indicate that there were improvements in the IC in the components of physical fitness (cardiorespiratory fitness, speed, and agility) and mental health indicators (total difficulties, emotional symptoms, problems with peers, and prosocial behavior) after a school physical education program in comparison with the CC. Concerning the prevalence of responders between groups, it was found differences in cardiorespiratory fitness (CC: 33.33%; IC: 65.38%), agility (CC: 36.66%; IC: 73.07%), speed (CC: 43.33%; IC: 79.16%), emotional symptoms (CC: 28.57%; IC: 50.00%), and prosocial behavior (CC: 17.14%; IC: 46.87%). Conclusion: It is reinforced that well-planned physical education classes and simple intervention programs can be adopted at the school level and are capable of promoting children's physical and mental health.