Individuals with Down syndrome (DS) have higher rates of obesity. In the general population green tea extracts, and in particular epigallocatechin gallate (EGCG), have been studied for their antiobesogenic effects. The aim of this study is to elucidate the effect of EGCG on body weight in young DS adults and whether it could be related to changes in lipid profile.In the context of a double-blind phase II clinical trial comparing the effect of EGCG to that of placebo, the body composition of 77 young adults with DS was analyzed through bioelectrical impedance analysis. Lipids were analyzed using standard laboratory procedures. The factors tested in the ANCOVA model for the differences from baseline were treatment, sex as well as their interaction as independent variables. Baseline values were included in the models as covariates.Individuals receiving placebo showed an increase in body weight and body mass index (BMI) that was not detected in those with EGCG treatment. EGCG effect on body composition was mainly observed in males, with significant differences between the EGCG and the placebo group after 12 months for weight (estimated adjusted mean difference (AMD) = -2.34, 95% CI = [-4.21, -0.48]; p = 0.015) and body fat (estimated AMD = -1.23, 95% CI = [-2.43,-0.04], p = 0.043). The changes detected in body composition were associated with changes in lipid profile.Our results suggest that EGCG could have a modest beneficial effect on weight management in DS. Furthermore, EGCG has also a sex-dependent effect on lipid profile that is related to changes in body mass and composition.