Red blood cells containing hemoglobin S are less deformable than normal erythrocytes and have a major effect on the viscoelasticity of blood. This alteration in rheology increases the impedance to flow, leading to an increase in RBC aggregation and reduction in oxygen saturation, which induces further sickling and occlusions in the microcirculation. Patients with sickle cell disease (SCD) can experience severe complications, such as acute pain and stroke. Automated red blood cell exchange transfusion, or erythrocytapheresis, is used with homozygous SCD (Hb SS) to replace sickled cells with normal cells, thereby decreasing the percentage of sickle hemoglobin (%Hb S) and maintaining a net balance in iron accumulation. These patients received monthly erythrocytapheresis with a goal to maintain a pre-pheresis %Hb S at less than 30%. In this study, viscoelastic parameters were used to quantify the effectiveness of this therapy for six patients undergoing chronic erythrocytapheresis. Whole blood viscosity, elasticity and relaxation time at oscillatory strains of 0.2, 1 and 5, and hematocrit and %Hb S were measured prior to erythrocytapheresis and 15 minutes after completion and compared with normal reference values at the patient's hematocrit. This study confirms the beneficial effects on viscosity, elasticity, and relaxation time of erythrocytapheresis.