Background: The major forms of sickle cell disease are characterized by hemolysis. The extent of this hemolysis may itself depend on the form of the disease even in the steady-state. This study aims to compare the indirect bilirubin level between the homozygous and beta plus sickle cell anemia (SAFA2) in the steady-state conditions. Material and methods: Fifty subjects of each forms, homozygous and beta plus sickle cell anemia were enrolled in a comparative hospital-based cross-sectional study from April 2008 to May 2008 at the laboratory of the university hospital of Yopougon, Ivory Coast. Subjects of each form awaiting their visits were selected from the database of the patients regularly followed in the clinical hematology department of Yopougon University Hospital. During their visits, clinical and socio-demographic data were collected, and a blood sample was also taken to carry out biological examinations. Blood count and bilirubin testing were performed by using Sysmex Kx-21™ and BioMérieux KONELAB-20™, respectively. Data were analysis in the software Statistical Product and Service Solutions version 12.0. Shapiro test was used to verify data normality and Student t-test for the comparison of parametric data means or Mann-Whitney’s independent test for none-parametric data. Pearson Chi square tests or Yate’s correction test for continuity where the first test was not appropriate. The threshold of statistical significance was set at p ≤ 0.05. Results: The median Hb was higher in SAFA2 patients compared to homozygous SSFA2 patients 10.7 g/dL [IQR = 8] vs 7.3 g/dL [IQR = 7]; p < 0.001. In contrast, the median of indirect bilirubin was lower in SAFA2 patients compared to SSFA2 patients 5.6 μmol/L [IQR = 10] vs 15.1 μmol/L [IQR = 13], p < 0.001. The ratio of these two medians shows that subjects SAFA2 hemolysis 2.7 times less than the homozygous subjects SSFA2 in the steady-state. Out of the one hundred subjects, indirect hyperbilirubinemia defined as indirect bilirubin median > 14 μmol/L was higher in men than in women 79.2% vs 20.8%, p = 0.01 whereas patients age groups was not associated to indirect hyperbilirubinemia, p = 0.4. Conclusion: Our data suggest that the hemolysis is higher in subjects SSFA2 than SAFA2 subjects in the steady-state. This marked chronic hemolysis of SSFA2 subjects must be taken into account when it comes to give a comprehensive care to these subjects.