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Objective: This study aimed to assess the mediation effects of lean mass and fat mass on the relationship between body mass index (BMI) and handgrip strength (HGS) in adolescents., Method: The sample included 118 adolescents (60 girls) aged 10-14 years. Body composition, determined from lean mass (LM) and fat mass (FM), was measured by dual-energy x-ray absorptiometry. HGS was measured using a digital dynamometer. Moderate-to-vigorous physical activity and sexual maturation, treated as covariates, were evaluated by accelerometry and pubic hair development, respectively. Spearman correlation and simple mediation analysis were used for statistical analysis., Results: A positive relationship was observed between BMI and HGS (rho = .364, p < .001), BMI and LM (rho = .466, p < .001), LM and HGS (rho = .784, p < .001), BMI and FM (rho = .907, p < .001), and FM and HGS (rho = .291, p = .001). LM was the only significant mediator of the relationship between BMI and HGS., Conclusion: Only LM mediated the association between BMI and HGS, almost entirely explaining the relationship. The findings reinforce the need to include LM measurements in routine strength testing. Furthermore, strategies focused on LM development may be promising in preventing low muscle strength in adolescents., (© 2023 Wiley Periodicals LLC.)