Background: Sickle cell anaemia (SCA) is a genetic disorder which can be complicated by haemolytic, vaso occlusive and thrombotic processes. Antithrombin III (ATIII) is a naturally occurring anticoagulant with anti inflammatory properties. The objective of this study was to determine the level of ATIII in individuals with SCA and to assess its role in vaso-occlusive crisis. Methods: This was an observational cross sectional study in which 60 adult HbSS (34 in steady state and 26 in vaso-occlusive crisis) subjects and 60 apparently healthy sex and age matched controls were recruited. Haemoglobin (Hb) electrophoresis of subjects and controls was determined using Hb electrophoresis. Nine and a half (9.5) milliliters of blood, divided into two aliquots of 4.5mls (in 0.5mls of tri sodium citrate for coagulation studies) and 5mls (in EDTA containing bottle for full blood count) was obtained. Quantitative assessment of antithrombin III by chromogenic assay with Factor Xa was carried out using Diachrom ATIII test kit. Prothrombin time, Activated partial thromboplastin time, Haematocrit, Total WBC and Platelet count were assessed using standard protocol. SPSS (version 13 for windows) was used for data analysis. A p value of <0.05 was considered significant.