Sickle cell disease is an hereditary hemoglobinopathy syndrome which provokes deglobulization crisis and infectious complications. These infectious diseases may be due to a permanent activation of the immune system. The aim of our study was to explore alternative pathway by measuring C3 complement and the classical pathway by C4 complement. The level of immunoglobulins IgA, IgG and IgM was also measured in the subjects sera. Thirty homozygous sickle cell anemia (SS), 25 heterozygous (AS) and 34 controls subjects (AA) were recruited in the Hôpital d'Enfants Albert Royer (HEAR), Fann hospital and Centre National de Transfusion Sanguine (CNTS). Radial Immunodiffusion (RID) technics using specific antisera for C3c, C4c, IgA, IgG and IgM were used in our study. Homozygous SS proved an increase level of IgA (50%, p < 0.003) and IgG (47%, p < 0.003), unlike of IgM level. The C3c complement decrease significantly in (27%) of homozygous SS patients (p < 0.0005) unlike of C4c level. This low level of C3 and IgG in sickle cell homozygous patients can explain the higher susceptibility to infection in these patients. Normal level of C4 and low level of C3 show activation of alternative pathway. Heterozygous AS showed a normal level of C4, C3 and immunoglobulins. Our results suggests a direct involvement of the complement system in sickle cell disease and the depletion of C3 registered was a possible cause of increased susceptibility to infections in patients with homozygous sickle cell anemia.