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Objectives: To ascertain the prevalence of transfusion transmissible infections (TTIs) across diverse donor groups in the Najran province. Additionally, to establish a potential association between the development of TTI and the donors' blood group, as determined by the ABO/Rh blood grouping system., Methods: Blood donation data of 4120 donors, spanning from January to December 2020, were retrospectively reviewed. The blood were screened for TTI markers, including hepatitis B surface antigen (HBsAg), anti-hepatitis B core (anti-HBc), anti-hepatitis C virus (anti-HCV), anti-human immunodeficiency viruses 1 and 2 (anti-HIV1&2), anti-human T-lymphotropic virus types 1 and 2 (anti-HTLV-1&2), and syphilis antigen., Results: Positive TTI markers were detected in 10.9% of the donors. The most detected TTI marker was anti-HBc (8.9%), followed by HBsAg (0.7%). Other markers were individually detected in <1% of the donors. Anti-HBc-positive was significantly elevated among non-Saudi blood donors. There was an association between age groups and anti-HCV ( p =0.002), anti-HTLV ( p =0.004) and syphilis antigen ( p =0.02) markers positivity. The AB positive blood group exhibited the most positivity for TTI markers, followed by O positive blood group. Similarly, association was found between ABO group and HBsAg ( p =0.01), anti-HBc ( p =0.001), and anti-HCV ( p <0.001) markers positivity., Conclusion: Emphasis on implementing robust screening measures for donated blood is underscored by this study. There is the need for future study to extensively evaluate TTI status to enhance our understanding of the trend in TTI., (Copyright: © Saudi Medical Journal.)