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Background: Transfusion is critical in the management of sickle cell disease (SCD) complications. The resultant alloimmunization to RBC group antigens is a major complication of allogeneic blood transfusion and generally presents significant challenges in the management of SCD patients. Aim: To measure the frequency of the occurrence of the alloimmune markers in sickle cell disease and to investigate its predicators. Subjects and methods: This cross-sectional study included 50 children and young adults with SCD, all patients were subjected to detailed medical history thorough clinical examination. Laboratory investigations included complete blood count, markers of hemolysis and serum ferritin. The D, C, c, E, e, M, NJKa and JKb antigens were typed using monoclonal antisera. Fya, Fyb, Jka, Jkb, S, s and Anti Lua antigens were typed by commercially prepared polyclonal anti- human sera. Antibody screening was performed using Ortho screening panel. Results: The study Sickle SS was the most common type of SCD representing more than half of the recruited patients. Frequency of antibody positive screening among SCD was 16%. Comparison between SCD patients with positive and those with negative antibody screening showed that higher frequency of positive antibody screening in those with SBþ than those SS and SB0. Patient with positive antibodies screening were significantly older when they received their first blood transfusion and had lower transfusion index (p=0.037) than those with negative antibodies screening (p=0.013). There were no significant difference between patients with positive and those with negative antibodies screening as regards age, gender, transfusion frequency and as regards comorbidities; painful crisis (p=0.117), stroke (p=0.398), ACS (p=0.363). Conclusion: The distribution of the blood group antigens in patients with SCD has important clinical significance especially those who often require regular blood transfusion and who may have developed multiple antibodies. The resultant alloimmunization is serious necessitates early recognition and management. [ABSTRACT FROM AUTHOR]