Individuals with Down syndrome (DS) exhibit reduced aerobic capacity with reduced peak heart rate (HRpeak). This condition is often coexistent with higher level of obesity compared to individuals without DS. The purpose of this study is to investigate the effects of obesity and Down syndrome (DS) on peak heart rate (HRpeak) and peak oxygen consumption (VO2peak) in children and adults both with and without intellectual disabilities (ID)s. VO2peak and HRpeak from individualized treadmill tests on 654 individuals were analyzed. Body mass index was used to categorize individuals' weight status using standard cut-offs. DS groups had the lowest HRpeak (167 bpm +/- 14, p < 0.05) compared to individuals with (183 bpm +/- 12) without ID (187 bpm +/- 12). Obesity did not affect HRpeak among adults and children with DS. VO2peak was lower among individuals with DS (25.2 mL/kg/min +/- 63, p < 0.05) when compared individuals with (37.0 mL/kg/min +/- 10.5) and without ID (36.1 mL/kg/min +/- 10.4). Obese adults with DS had lower VO2peak (24.3 mL/kg/min +/- 6.9, p= 0.001) compared to the normal weight (26.7 +/- 7.1 mL/kg/min) and overweight groups (27.0 mL/kg/min +/- 6.1) with DS. Conversely, in children, obesity level did not impact VO2peak in individuals with DS. Our results suggest that DS attenuates both VO2peak and HRpeak, regardless of obesity status and age group. However, obesity was associated with lower VO2peak in all adults, but not in children with DS.