Objective: The aim of this study was to determine the seroprevalence of HIV, the hepatitis B and C viruses, and syphilis as well the risk factors for these diseases among blood donors in Bangui, Central Africa Republic. Materials and Methods: This cross-sectional study examined samples from donors giving blood in August and September, 2013. HIV1/2 antibodies was screened with the Determine and Unigold HIV tests. Hepatitis B surface antigens were detected by sandwich immunochromatographic methods (DIAspot HBsAg test), and antibodies to HCV by the DIAspot test strip. Syphilis was diagnosed with the VDRL and TPHA methods (Omega Diagnostic, UK). The Chi(2) test was used for statistical analysis. Results: The study included samples from 551 individuals, 350 (63.52%) of whom were frequent volunteer donors. In all, 132 (23.95%) were infected with at least one pathogen. The overall seroprevalence rate was 8.89% for HBV, 4.72% for HCV, 4.36% for syphilis, and 5.98% for HIV. Eight patients had two concomitant infections, with HIV-HBV the most common combination. Compared to long-term volunteers, first-time donors were more often infected by at least one of the pathogens we screened for, most especially HVB (OR = 5.06; 95% CI = 4.22-7.11) and syphilis (OR = 2.05; 95% CI = 2.02-7.44). Conclusion: Our findings indicate the high seroprevalence of transfusion- transmitted infections in blood donated in Bangui. The most common combined infections were HIV-HBV. The most common risk factor was a family history of HBV infection, and especially, mother-child transmission.