The contribution of sickle cell trait (SCT) to racial disparities in cardiopulmonary fitness is not known despite concerns that SCT is associated with exertion-related sudden death. We evaluated the association of SCT status with cross-sectional and longitudinal changes in fitness and risk of hypertension, diabetes and metabolic syndrome over 25 years among 1,995 African Americans (56% women, 18 to 30 years old) in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Overall, the prevalence of SCT was 6.8% (136/1,995) in CARDIA and over 25 years, 46% (738/1,590), 18% (288/1,631) and 40% (645/1,611) of all participants developed hypertension, diabetes and metabolic syndrome, respectively. Compared to participants without SCT, participants with SCT had similar baseline measures of fitness in cross-section, including exercise duration (535 vs. 540 sec, p = 0.62), estimated METs (11.6 vs. 11.7, p = 0.80), maximum heart rate (174 vs. 175 beats/min, p = 0.41) and heart rate at 2 minutes recovery (44 vs. 43 beats/min, p = 0.28). In our secondary analysis, there was neither an association of SCT status with longitudinal changes in fitness nor an association with development of hypertension, diabetes or metabolic syndrome after adjustment for sex, baseline age, BMI, fitness and physical activity. SCT is not associated with reduced fitness in this longitudinal study of young African American adults suggesting that the increased risk for exertion-related sudden death in SCT carriers is unlikely related to fitness. SCT status also is not an independent risk factor for developing hypertension, diabetes or metabolic syndrome.