ABSTRACT Background Sickle cell anemia (SCA) is characterized by recurrent pain, chronic hemolysis, autonomic imbalance, and progressive vascular dysfunction. In sub‐Saharan Africa, where access to disease‐modifying therapies remains limited, identifying modifiable behavioral determinants such as physical activity (PA) is of particular clinical relevance. This study examined the associations between objectively measured daily step count and clinical, biological, hemorheological, vascular, and autonomic parameters in adults with SCA. Methods Ninety‐eight adults with SCA were stratified into tertiles according to accelerometer‐derived daily step count. Pain burden, renal indices (albuminuria and estimated glomerular filtration rate eGFR), hematological and hemorheological parameters, arterial stiffness (carotid–femoral pulse wave velocity), and heart rate variability were assessed. Results Higher daily step counts were associated with less frequent intense pain, reduced blood viscosity, and a higher hematocrit‐to‐viscosity ratio. More active participants also exhibited lower arterial stiffness and greater parasympathetic modulation. A graded, linear pattern was observed across tertiles for most outcomes. Although eGFR was positively associated with physical activity, this relationship was largely explained by age differences between groups. Discussion Greater daily physical activity is associated with a more favorable clinical and physiological profile in adults with SCA. While causality cannot be inferred, daily PA may represent both a marker of health status and a potential target for preventive strategies in this population. Trial Registration: UMIN000042826
Diaw et al. (Fri,) studied this question.