Introduction: Sickle cell disease is a public health problem in the Republic of Congo where the prevalence of sickle cell trait is estimated at 1.25%. The objective of this study is to describe the variations of hematological and biochemical parameters of hemolysis in sickle cell patients in critical and inter-critical periods. Methods: This is a descriptive cross-sectional study including sickle cell patients followed regularly at the National Reference Center for Sickle Cell Disease (CNRDr) from November 2019 to March 2020. A sample of 167 patients (sickle cell subjects in crisis and in steady state as well as control subjects) was randomly selected during the study period. The blood count was performed using a Sysmex-XN 350 automated system and the biochemical parameters were determined using the Cobas e 311 automated system. Statistical analysis was performed with SPSS version 22 software. Results: The study showed that the mean cholesterol level in controls was 4.16 ± 0.77 ul compared with 9.64 ± 4.34 ul in sickle cell crisis subjects. Hb and HCT levels were significantly higher in controls compared with sickle cell subjects in crisis. During crisis, total bilirubin, direct bilirubin, triglycerides, LDH, AST, and CRP were significantly elevated. Hematological parameters such as Hb and HCT were elevated in controls, while the mean WBC value and RET were higher in sickle cell patients in steady state. The mean values of the biochemical parameters were higher in sickle cell patients in steady state. Conclusion: Evaluation of the influence of sickle cell trait on biochemical and hematological parameters showed significant differences between sickle cell and control subjects.