The present study aimed at comparing fat and lean masses between children and adolescents with and without Down syndrome (DS) and evaluating the presence of sexual dimorphism. Total and regional fat and lean masses were assessed by dual energy X-ray absorptiometry (DXA) and the percentage of body fat (%BF) by air-displacement plethysmography (ADP) in 31 participants with DS and 32 controls. Waist circumference (WC) was also measured. Analysis of covariance and the Student's t-test were used to compare variables between groups and between sexes within the same group. There were no significant differences in %BF, WC or body mass index (BMI) between groups. Females with DS showed higher fat and lean masses in the trunk, and lower fat and lean masses in the lower limbs compared with females without DS (all p≤0.05). Males with DS showed higher fat masses in the whole body and upper limbs, and lower lean masses in the whole body and lower limbs compared with males without DS (all p≤0.05). Females in both groups showed higher levels of fat, and lower levels of lean than did their respective males (all p≤0.05). Youths with DS showed higher fat and lower lean than their non-DS peers. The increased truncal fat in females with DS might indicate a higher risk of metabolic syndrome in this group. Sexual dimorphism in youths with and without DS was very similar. BMI, WC and %BF were not effective indicators of increased risk in youths with DS.