Background The transfusion of blood and blood components has a significant role in healthcare services. However, it remains a possible risk factor for blood-borne infections. The present study was conducted to assess the prevalence of serological markers of common blood-borne infections among the blood donor population of Afghanistan. Methodology This was a cross-sectional study based on retrospectively collected data over a period of six years from 284 blood centres across 34 provinces of Afghanistan. Every blood donor’s sample was tested by rapid immunoassays for the serological markers of blood-borne infections namely hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV), anti-human immunodeficiency virus 1/2 (anti-HIV1/2), and anti-Treponema pallidum (anti-TP). Results All blood donors during the study period were males. The majority of blood donations were from the family replacement category 56.93% (n = 544,568). The overall pooled prevalence of blood-borne infections was 4.36% with a comparatively higher percentage in family replacement donors 4.88%. The seropositivity for HBsAg, anti-HCV, anti-HIV1/2, and anti-TP was 2.95%, 0.81%, 0.04%, and 0.54%, respectively. Conclusion Complete reliance on voluntary blood donors and screening with quality assured highly sensitive assay is recommended to ensure blood safety in the country.

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