The vascular wall participates in the pathogenesis of sickle cell disease (SCD). Circulating Endothelial progenitor cells (cEPCs) also play a key role in the vascular pathology of SCD, including the painful crisis. In previous investigations, reduced levels of cEPCs were found in conditions in which vascular injury is implicated such as myocardial infarction. The aim of this research is to study the role of cEPCs in the vascular pathology of SCD. cEPCs were enumerated using flow cytometry with the Flow Activated Cell Sorting machine (FACS). To differentiate the various genotypes-SS, SC, AS, AC and AA, Hb Electrophoresis was employed. Results showed that the median % cEPCs (CD34+/VEGF-2+) was lower in patients with SCD [0.555(0.4, 0.765)] than in healthy controls [(1.08(0.87, 1.39) (p=0.001)]. Patients in crisis had a higher cEPCs (0.65+0.39) than those in steady state (0.59+0.28) (p=0.522). SS group recorded the highest mean GGT (73.66+73.35). Only total cholesterol demonstrated a positive correlation (r=0.378, p=0.00814) with cEPCs in subjects; a trend unseen in healthy controls. Patients’ WBC, Hb and Liver enzymes- ALT, GGT, ALP showed no correlation with cEPCs. In healthy controls though, WBCs showed an inverse correlation with cEPCs (r=-0.6293, p=0.0003). SCD is as much a disease of endothelial dysfunction as it is a hemoglobinopathy that triggers erythrocyte polymerization: cEPC is a surrogate bio-marker for vascular function in SCD patients. The results suggest that SCD patients have depleted cEPCs compared with healthy controls. Oxidative stress, Nitric oxide activity, loss of CD133 during homing could influence progenitor cell populations. Total cholesterol positively correlates with cEPCs. High total cholesterol could spell the onset of painful crisis. Liver enzymes are not related to cEPCs correlatively even though the liver is involved in endothelial injury in SCD patients. SS individuals tend to have a high GGT. Overall, we have shown the direct correlation between total cholesterol and cEPCs in sickle cell patients.