Because of the metabolic changes induced by a physical activity, the hemorheological properties of patients with sickle cell anemia could be further impaired and increase the risks for vaso-occlusive complications. However, few studies suggest that moderate physical activity could be beneficial rather than harmful in patients with sickle cell anemia (SCA). However, the definition of what can be considered as a moderate physical activity in SCA patients is imprecise. The present study tested the effects of a short incremental cycling exercise test conducted until the first ventilatory threshold on different biomarkers. Hematological and hemorheological parameters were compared between 8 patients with SCA and 13 healthy subjects (CONT) before, immediately after the end of the exercise and at 12, 36 and 60 hours after the exercise. We observed no significant hematological or hemorheological alteration induced by the exercise in the two groups. However, the exercise resulted in a delayed improvement of the red blood cell disaggregation threshold at 36 and 60 hrs after exercise in the SCA group which was paralleled to the decrease in the platelet count in this group. The present study suggests that such an exercise might be beneficial for microcirculatory blood flow.