Introduction: Chronic hepatitis B virus (HBV) infection leads to considerable morbidity and early mortality. Development of chronic HBV infection can be prevented by a three to four dose schedule of Hepatitis B vaccines in immunocompetent infants. However, HIV exposed uninfected infants (HEU) are thought to exhibit an attenuated immune response to some vaccines. In addition, a significant proportion of pregnant women in Nigeria have antibodies to HBV, specifically Hepatitis B surface antibodies (HBsAb). Maternal antibodies inhibit infant immune responses in some instances. Objective: To estimate the effect of antenatal and perinatal exposure to maternal HIV, and the effects of maternal HBsAb on the immune response of Nigerian infants to hepatitis B vaccine. Methods: Using a retrospective cohort design, we determined the relationship between infant HIV-exposure status, and infant exposure to detectable concentrations of maternal HBsAb, and infant immune response to Hepatitis B vaccine separately using general linear models adjusted for potential confounders. Subsequently, we used Fisher’s Exact tests to compare the proportion of infants with HBsAb concentrations above 10mIU/mL: for HEU as compared to HIV unexposed uninfected infants (HUU), and for infants exposed to detectable concentrations of maternal HBsAb as compared to infants unexposed to detectable concentrations of maternal HBsAb at 24 and 52 weeks of age separately. Results: We found HIV exposure to be associated with infant immune response to hepatitis B vaccine at birth, Weeks 4 and 52 (P<0.0001, P=0.05 and P<0.0001) and also to be associated with the proportion of infants with HBsAb concentrations ≥ 10mIU/mL at Week 52 (P=0.04). Exposure to detectable concentrations of maternal HBsAb was also associated with infant immune response at Weeks 24 and 52 respectively. Conclusion: Though antenatal and perinatal exposure to HIV, and to detectable concentrations of maternal HBsAb were found to be associated with infant immune response to hepatitis B vaccine, these exposures did not appear to attenuate immune response. In addition, differences observed in the proportion of infants with HBsAb concentrations ≥ 10mIU/mL were small and do not appear to be clinically relevant.