INTRODUCTION: Blood-born infections are common during unsafe blood transmission. There is a paucity of information on their burden at blood banks of the Democratic Republic of Congo (DRC). Therefore, this aimed to determine the prevalence and factors associated with human immunodeficiency virus (HIV), hepatitis B and C viruses, and syphilis infections among blood donors at the Butembo blood bank, North Kivu, DRC. METHODS: this study used the dataset of the Butembo blood bank using a step-wise approach. Human immunodeficiency virus, hepatitis B and C viruses, and syphilis infections were determined using serological testing. Logistic regression models were performed to explore factors associated with blood-borne infections. RESULTS: in total, this study enrolled 12208 participants among which 5.8% (n=608) had blood-borne infections. Most of the participants with blood-borne infections were female (67.3%) with a mean age of 22.7 years and standard deviation of 5.3. The overall seroprevalence rates of hepatitis C and B viruses, syphilis and HIV among blood donors were 34.9% (n=212), 32.1% (195) 25.3% (n=154), and 7% (n=47) respectively. Factors associated with blood-borne infections among blood donors included being female (aOR: 3.53, 95% CI: 1.16-8.19; p = 0.030), attaining a low level of education (aOR: 5.12, 95% CI: 1.59-1.39; p = 0.016), living in rural areas (aOR: 4.33, 95% CI: 1.277.34; p = 0.028), having received prior treatment for STDs, being married (aOR: 3.87, 95% CI: 1.37-6.66; p = 0.010), being younger than 30 years old (aOR: 6.44, 95% CI: 2.51-13.4; p=0.007), and being employed (aOR: 1.95, 95% CI: 1.60-3.51; p=0.006). Attaining a university level of education showed a protective effect against hepatitis B virus (aOR: 0.26, 95% CI: 0.12-0.71; p = 0.018) and syphilis (aOR: 0.65, 95%CI: 0.09-0.85; p=0.013) among blood donors. CONCLUSION: the prevalence of HIV, hepatitis B and C viruses, and syphilis infections among blood donors is high. Our findings recommended a proper screening of blood-borne infections at blood banks for effective prevention and control of transfusion-transmitted diseases.