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Erythrocyte antigens, particularly those which give rise to different blood group systems, are potentially known to perform as receptor sites for different types of disease-causing agents. It is for this reason that this study was carried out to determine the distribution of different blood groups and how susceptible they are to human immunodeficiency virus (HIV) infection. For this study, data were retrieved from different blood bank registers at 4 major blood banks in Ekiti State (National Blood Transfusion Services, Ado, State Specialist Hospital, Ikole, State Specialist Hospital, Ijero, State Specialist Hospital, Ikere. All in Ekiti State). Demographic data such as age and gender were collected on 2388 individuals who were recruited at the above stated facilities over a 2-year period. Their blood groups (Rhesus and ABO) and HIV status were equally recorded. Results of the ABO blood group analysis of the subjects showed that Blood Group O had the highest population (78.2%) while blood Group AB had the lowest (0.9%). The percentages of Rhesus positive and negative persons observed in this population were 94.7% and 5.3%, respectively. The total sero-prevalence of HIV infection was 0.81%. However, there was no significant difference in the prevalence of HIV among the different ABO and Rhesus blood types. This study revealed no association between ABO and Rhesus blood groups and HIV infection., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)