PURPOSE: Sickle cell disease (SCD) significantly affects physical functioning. We examined physical activity (PA) patterns in children with SCD versus a national sample and factors associated with PA and participation in physical education and organized sports. METHOD: One hundred children with SCD completed a 58-item survey with questions from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) Physical Activity Questionnaire and others on physical education and sports, disease impact, and physical functioning. RESULTS: Compared with NHANES participants, more children with SCD (67 vs 42%, p < .01) reported doing at least 10 min of moderate-to-vigorous intensity PA (MVPA)/week. Children with SCD also reported spending more days in MVPA (2.3 vs. 1.4 days/week, p < .01). However, fewer reported spending (3) 60 min/day in either vigorous PA (VPA) (24 vs. 43%, p = .01) or MVPA (17 vs 23%, p < .01). In addition, 90% and 48% of children with SCD participated in physical education and sports, respectively. Greater disease impact on PA and physical functioning were associated with lower participation. CONCLUSION: Children with SCD are active at moderate to vigorous intensity for shorter durations. Negative personal beliefs about disease impact and poor physical functioning represent barriers to PA in SCD.