OBJECTIVE: To examine heart rate recovery (HRR) as an indicator of autonomic nervous system dysfunction after maximal exercise testing in children and young adults with sickle cell anemia (SCA). STUDY DESIGN: Recovery phase heart rate (HR) in the first 5 minutes after maximal exercise testing in 60 subjects with SCA and 30 matched controls without SCA was assessed. The difference between peak HR and HR at both 1-minute (DeltaHR1min) and 2-minutes recovery was our primary outcome. RESULTS: Compared with controls, subjects with SCA demonstrated significantly smaller mean DeltaHR1min (23 beats per minute [bpm], 95% CI 20-26 vs 32 bpm, 95% CI 26-37, P = .006) and the difference between maximal HR and HR at 2 minutes (39 bpm, 95% CI 36-43 vs 48 bpm, 95% CI 42-53, P = .011). Subjects with SCA also showed smaller mean changes in HR from peak HR to 1 minute, from 1 minute to 2 minutes, and from 2 through 5 minutes of recovery by repeated-measures testing. In a multivariable regression model, older age was independently associated with smaller DeltaHR1min in subjects with SCA. Cardiopulmonary fitness and hydroxyurea use, however, were not independent predictors of DeltaHR1min. CONCLUSIONS: Children with SCA demonstrate impaired HRR after maximal exercise. Reduced postexercise HRR in SCA suggests impaired parasympathetic function, which may become progressively worse with age, in this population.