Background: Allo-immunization is an immune response to foreign antigens after exposure to genetically different cells or tissues. Allo-immunized patients with sickle cell disease (SCD) appear to experience worse survival compared to non allo-immunized patients. Therefore, to contribute to the management of patients living with SCD and improve the blood transfusion process, we aimed to determine the frequency of allo-immunization in SCD's patients. To realize this study, we carry out a cross sectional study in one Hospital of Douala-Cameroon. Method: Plasma was prepared from collected blood sample, electrophoresis was done and depending on the migration on the gel; the type of electrophoresis was determine. Blood group ABO/Rh was done. After electrophoresis, depending on the result obtained those that was not homozygote (SS) and heterozygote sickle cell anemia (AS) was discarded. The check for irregular agglutinins was done using the indirect Coombs test. Clinical and biological characteristics of the different participants were studied and analyzed using a Statview statistical software. Result: We obtained 104 sickle cell patient, out of these we had 55% of positive RAI, with an average transfusion of 7.35. Also 83 patients were homozygote sickle cell anemia for a mean age of 15.75 years old (ranging from 1 to 52 years). The result obtained shows that the number of blood transfusion for homozygote sickle cell patient increases with age and that homozygote sickle cell patient received more blood transfusion than heterozygote patient. It can also be said that allo-immunization in these patients originate from the multiple blood transfusion received that were not fully compatible and that it affects more children (from 1 -15), they accounted for about 53.85% of the total population. Our result obtained implies that in the future, sickle cell patient will have difficulty in finding compatible blood for treatment and is a real problem since transfusion is the major standard of care for patient suffering from sickle cell anemia in Cameroon. The absence of treatment may lead to the death of the patient. To help reduced allo-immunization, extended compatibility test in all the red blood cell system and routinely screening for the presence of irregulars agglutinins may reduce the frequency of allo-immunization.