Introduction: Blood group antigens play an essential role in transfusion safety and in avoiding the risk of alloimmunization. The ABO, Rh and Kell blood group systems are the most clinically important. The aim of this study was to determine the frequency of ABO, Rh and Kell blood groups among blood donors in Brazzaville, Republic of Congo. Methods: This was a cross-sectional study conducted among blood donors in Brazzaville, republic of Congo, from June 2021 to November 2022. The blood samples were tested for ABO, Rh and Kell antigens by standard tube agglutination method. The statistical analysis was done using SPSS version 21.0. Results: A total of 350 participants were included, of which 258(73.7%) of donors were males and 92 (26.3%) females. The antigen frequencies of ABO and Rh(D) blood group system showed that O was the most prevalent blood group 46.8% followed by A (28.9%), B (16.9%), and AB (7.4%). The Rh-positive donors were more prevalent (94.86%) as oppose to the Rh-negative (5.14%). The most common Rh phenotype is the Dccee (64.86%) while the rarest phenotype is the dCcee (0.86%). The prevalence of K and k antigen was 0.9% and 99.1%, respectively. Conclusion: This study determined the phenotypic variability of ABO and Rh blood group antigens with low prevalence of Kell antigen. The extensive phenotypic status of Rh and Kell systems in blood donors is important for the efficient management of blood banks and transfusion services.