Hepatitis B virus co-infection with Hepatitis C virus and/or Hepatitis D virus is known to result in a more deleterious disease than chronic HBV mono-infection, resulting in faster disease progression to cirrhosis and hepatocellular carcinoma. This study aimed at determining the serological prevalence of Hepatitis C and D virus infections among chronic Hepatitis B virus carriers and the frequency of Hepatitis B e Antigen in a tertiary hospital in South-East, Nigeria. This is a cross-sectional study involving 72 consenting participants who are chronic Hepatitis B virus carriers. Blood samples were collected and serological analysis as well as Hepatitis B virus deoxyribonucleic acid quantification was carried out. The Hepatitis B virus/Hepatitis C virus co-infection rate was observed as 37.5% and Hepatitis B virus/Hepatitis D virus co-infection occurred at a frequency of 2.8%. The Hepatits B viral load and serum alpha fetoprotein levels were observed to have significantly higher median values among the Hepatitis B virus/HCV co-infected participants than among the mono-infected participants (P<0.05). The median Hepatitis B viral load and serum alpha fetoprotein level were also higher among the Hepatitis B virus/Hepatitis D virus co-infected participants than the Hepatitis B mono-infected participants but the difference in viral load was not statistically significant. However, the difference in serum alpha fetoprotein level was observed to be statistically significant. These findings suggest the possibility of a more serious outcome of chronic Hepatitis B virus infection within the study area. Hence, there is need for regular monitoring and aggressive antiviral treatment.