Objective Irisin is a novel myokine that seems to mediate the beneficial effects of exercise. Levels of circulating irisin before and after an 8‐month physical activity program (PAP) in school‐age children were evaluated. Methods Irisin and leptin were measured at baseline and at follow‐up among 85 children with different BMI. Results Of the 85 children (mean age 8.9; 47% female), 25 children had normal weight, 23 were overweight, and 37 had obesity. We observed no significant difference in irisin serum levels between boys and girls. Irisin was positively associated with BMI before and after the PAP (rbefore = 0.42; rafter = 0.37, P < 0.001), with the highest levels in children with obesity. There was a slight decrease of circulating irisin after PAP, but this decrease was not of statistical significance. We observed a high and positive association between irisin and leptin levels before and after the PAP (rbefore = 0.78; rafter = 0.82, P < 0.001). Moreover, changes in leptin correlated with changes in irisin (r = 0.72, P < 0.001). Conclusions Circulating irisin is positively linked to BMI and leptin in school‐age children, supporting the notion that that irisin is produced by adipose tissue. As in previous reports, this study failed to observe changes in irisin levels after exercise, likely because higher irisin levels are produced only during exercise.