BACKGROUND: Sickle cell disease (SCD) is characterized by vaso-occlusive events and organ damage which form important causes of morbidity and mortality. Although protein C, a naturally occurring anticoagulant has been demonstrated to be deficient in sickle cell patients, the impact of hypercoagulable states and thrombosis on sickle cell disease still remains uncertain. OBJECTIVE: The objective of this study was to determine the protein C (PC) levels of the sickle cell patients and to explore the relationship between protein C levels and vaso-occlusive events as well as related complications. SUBJECTS, MATERIALS AND METHODS: A cross-sectional study comprising sixty one sickle cell subjects and thirty healthy haemoglobin-AA control subjects was carried out. Protein C antigen (quantitative) and activity (qualitative) levels were assayed using enzyme linked immunosorbent assay and a microtitre plate adjustment of the protac method respectively. Haematological parameters were measured with the haematology automated analyzer.