Introduction: “Obesity” is considered a feature of youth with DS but whether “low physical fitness” is also a feature is unknown. Objective: The aim of this case-control study was to compare the levels of fatness and fitness in adolescents with and without DS. Methods: Participants included 17 (5 girls) adolescents with DS aged 12-18 years and a control group of 94 (45 girls) adolescents without DS aged 12-16 years. The ALPHA health-related fitness test battery for children and adolescents was selected to assess fatness and fitness in both groups. Results: There were no differences in levels of fatness between groups (all P > 0.27). Adolescents with DS had lower levels of fitness in all the tests than adolescents without DS (all P < 0.001). Conclusion: Adolescents with DS have similar levels of fatness and lower levels of fitness than their peers without DS.