Hepatitis B virus (HBV) remains highly endemic in sub-Saharan Africa, where perinatal and early childhood transmission contribute substantially to chronic infection. Although routine infant vaccination is widely implemented, birth-dose coverage remains inconsistent in many settings. This study carried out in strict compliance with ethical rules, evaluated serological markers of HBV exposure and vaccine-induced immunity among fully vaccinated infants in Cameroon. It was a cross sectional study involving 9 to 15 months old hepatitis B fully vaccinated and HIV negative infants living in the towns of Douala and Yaoundé. Infants born to mothers known to be HBsAg-positive were excluded. Serum samples were tested for HBV serological markers, using lateral flow immunochromatography [1] techniques and indirect elisa [2,3]. Whereas 84.85% (56/66) of theses infants achieved seroprotective anti-HBs levels, 16.67% (11/66) was Anti-HBc seropositive. Overall, 63.64% of these anti-HBc seropositive infants were significantly less likely to demonstrate seroprotection compared with anti-HBc seronegative infants (adjusted OR 30.3; 95% CI 5.58–164.75). These results that highlights the association between anti-HBc positivity and reduced seroprotection, warrants further investigation, including molecular testing to distinguish passive maternal antibody transfer from occult or resolved infection. Strengthening perinatal HBV prevention strategies remains critical to achieving elimination targets.