Background. Human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C virus (HCV) are transfusion-transmittable infections (TTI). They currently constitute a major public health problem in Cameroon, like in other developing countries. Little is known about the seroprevalence of HIV, HBV, HCV, and syphilis among blood donors in northern region Cameroun. This study aims at filling the gap on the unknown sero-prevalence of those markers in blood donors. Methods. We conducted a cross-sectional study from June 04, to July 08, 2022 at the Garoua Regional Hospital Blood Bank (GRHBB). A total of 201donors were consecutively included and data on donor’s sociodemographic characteristics were obtained by the national program’s questionnaire. Serum samples from blood donors were tested using sensitive third generation Rapid diagnostic test (RDT) for presence of Hepatits B surface antigens (HBsAg), and antibodies to human immunodeficiency (HIV-1/2), Hepatits C (HCV) and Treponema pallidum; and quantitative enzyme-linked immunosorbent assays (ELISA) served for confirmation. Data were collected and entered into an Excel sheet and then exported to SPSS version 20.0 for analysis. Results. A total of 201 blood donors were identified and the sex ratio (male/female) was 7/1, with a mean age of 32.12 ± 8.4 years (range: 19 to 57 years). Of all blood donors, 35/201 (17.4%) were infested by at least one of the four TTIs. Among blood donors, HIV, HBV, HCV and syphilis were 5 (2.5%); 26 (12.9%); 1 (0.5%) and 5 (2.5%), respectively. Co-infection with HIV-Syphilis was 1 (0.5%); and HBV-HCV 1 (0.5%). Conclusions. This study has revealed the high prevalence of TTIs in blood donors who attended the Garoua Regional Hospital Blood Bank, identifying Hepatitis B as the greatest threat to blood safety in the North Region of Cameroon.