1 Introduction Sickle cell anemia (SCA) is caused by homozygous inheritance of the sickle cell mutation (βS) or heterozygous co-inheritance of βS and the β0 mutation, which results in production of sickle hemoglobin (HbS). In addition to chronic hemolytic anemia and recurrent episodes of acute debilitating vaso-occlusive pain, both acute and chronic end-organ damage are common in SCA; together, these manifestations lead to reduced physical functioning and decreased exercise capacity.