The ACE2 gene polymorphisms (rs143936283, rs146676783, and rs4646116) in infected and noninfected persons by SARS-CoV-2 in Burkina Faso. Our cross-sectional study population comprised 137 SARS-CoV-2 infected persons and 181 non-infected persons. Three ACE2 gene polymorphisms rs143936283, rs146676783, and rs4646116, were genotyped using the real-time PCR standard TaqMan allelic discrimination technique. The association between SARS-CoV-2 infection and the polymorphisms were evaluated by a binary logistic regression. There was no association between the polymorphisms rs143936283, rs4646116 haplotypes, and SARS-CoV-2 infection in our study population. However, in the female population, the heterozygous genotype CT of rs146676783 increased by two and half the risk (OR=2.58 95%CI (1.2-5.48), p= 0.014) of being infected by SARS-CoV-2. Additionally, carrying the homozygous minor allele (genotype TT) of rs146676783 increased by more than five and half the risk (OR=5.57 95%CI (1.64-18.78), p=0.006) of being infected by SARS-CoV-2 among females. This study showed that the ACE2 gene variant rs146676783 was associated with an increased risk of being infected by SARS-CoV-2 in females, suggesting a need for further investigation to contribute to a better understanding of the African COVID-19 enigma.