Abstract Sickle cell disease (SCD), caused by a mutation in the β-globin gene HBB, is widely distributed in malaria endemic regions. The prevalence of sickle cell trait and disease reaches up to 4.8-6% and 0.2% respectively, which is the highest among the Arab Gulf states. Omani population represents a variability of HbS genotype combinations with other Hb genotypes modify the clinical severity of the disease. The most prevalent sickling abnormality in Oman is Hb S/S (SCA) followed by Hb S/β-thalassemia. Omani children with SCD with high Hb F level had less severe disease. More than two-thirds of SCD cases were running a mild course of the disease due to the high prevalence of a-thalassemia trait. The severity index has been correlated with the early age of presentation, the absence of a-thalassemia trait and the lower level of HbF as well as to the existence of different β-globin gene haplotypes. S/ β0 presented with the same clinical severity of S/S while those with S/ β+ had some splenic function into adulthood and were more prone to splenic sequestration. The unique existence of HbS-Oman (a severe variant of sickle hemoglobinopathy) markedly increased the severity of the disease. Compound heterozygotes HbS-Oman resulted in very severe clinical manifestations with transfusion-dependency and hypersplenism early in life. This paper summarizes and reviews βs gene haplotypes in patients with sickle cell anemia (SCA) in Oman. Conflict of interest statement Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.) that might pose a conflict of interest in connection with the submitted article.