Despite the unicity of its genetic mutation, Sickle cell homozygosity presents different clinical features. Our objectives were to evaluate disease severity in Senegalese patients. Sixty (60) homozygous sickle cell patients were followed up monthly during one year and disease severity was assessed using the "severity index" (SI) which is resulting from epidemiologic, clinic and biological data. Mean age was 20.13, sex ratio was 0.87 and mean age of diagnosis was 9.8 years. 90% of patients presented vaso-occlusive crisis (2.53 per patient), 73.3% had infectious episodes (1.9 per patient), 69.3% had never been transfused and 25% of patients had presented chronic complications linked to anemia or ischemia. Mean hemoglobin value was 8.1 g/dl and mean Hb F was 8.2%. Low seric ferritin was found in 1.7% of patients. Benign form of homozygous sickle cell anemia (SI< or =6) was found in 48.3% of patients. Our data confirm the relative good tolerance of homozygous sickle cell disease in Senegal. The haplotype Senegal may play an important role but others host and environmental factors operate certainly because some severe cases were identified in our patients. The identification of all these factors might contribute to a better follow up of sickle cell disease.