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Haptoglobin is a protein involved in protecting the body from the harmful effects of free hemoglobin. The haptoglobin gene exhibits a polymorphism, and the different genotypes do not have the same capacity to combat the free hemoglobin effects. The present study aimed at determining the polymorphic distribution of haptoglobin in sickle cell patients (SCPs) from West Cameroon and their impact on the hematological parameters, as well as clinical manifestations of the disease severity. Haptoglobin genotype of 102 SCPs (SS) and 115 healthy individuals (60 AA and 55 AS) was determined by allele-specific polymerase chain reaction, and the complete blood count was determined using the AutoAnalyser. Results showed that the genotype Hp2-2 was significantly ( p  < 0.05) represented in SS patients (54%) than in controls AA and AS (27% and 29%, respectively), while Hp2-1 was mostly found ( p  < 0.05) in AS (42%) and AA (38%), against 15% in SS. The allelic distribution in SS patients was Hp 2 : 0.613, Hp 1S : 0.304, and Hp 1F : 0.084. In AA and AS controls, the proportions of the Hp 1 and Hp 2 alleles were similar (around 0.5 each), with 0.282 for Hp 1S and 0.218 for Hp 1F in AS and 0.283 for Hp 1S and 0.258 for Hp 1F in AA. The distribution of the haptoglobin genotypes did not reveal any significant difference across hematological parameters and clinical manifestations of disease severity in SCP and controls. SCP with Hp1S-1F genotype presented the highest level of hemoglobin. Although Hp2-2 was more frequent in SS patients, it appeared not to be related to the hematological parameters and to the disease's severity. Further investigations are necessary to explore the impact of Hp polymorphism such as antioxidant, lipid profile, and functionality of some tissues in SCP in Cameroon., Competing Interests: The authors declare no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Christian Bernard Kengne Fotsing et al.)