Aims: To evaluate Hepatitis B virus (HBV) infection treatment outcome using the levels of white blood cells, haemoglobin, platelets counts and other red cell indices of HBV positive treatment naïve, on treatment at 3- and 6-months subjects attending gastro-enterology clinic in Federal Medical Centre Asaba, Delta State, Nigeria Study Design: Cross-Sectional and longitudinal study. Place and Duration of Study: Federal Medical Centre Asaba (FMC) and Iykenson Medical and Diagnostic Co. Ltd, Awka. Federal Medical Centre, Asaba, between August 2019 and September 2020. Methodology: A total of one hundred and fifteen (115) adults aged 22 – 64 years participated in this study. The study sites for this work comprised of Federal Medical Centre Asaba (FMC) and Iykenson Medical and Diagnostic Co. Ltd, Awka. The cross-sectional study consists of fifty (50) confirmed hepatitis B negative subjects as negative controls whereas, the follow-up study consists sixty-five (65) treatment naïve HBV positive subjects which were followed-up at three and six months on treatment with tenovofir respectively. Four (4) of the participants (two in three months post treatment and two six months post treatment) dropped-out of the research due to time constraint. Blood samples were collected from the subjects in EDTA bottles and were used for the analysis of white blood cell (WBC count), haemoglobin concentration, packed cell volume (PCV), mean cell volume (MCV), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC) and platelet count (PLT). Statistical Package for social Science (SPSS) software version 26 was used in the analysis of data and P<.05 was considered statistically significant. Results: There were no significant difference (P>.05) in neutrophil, lymphocyte, eosinophil and monocyte in the study population among the four groups whereas, the level of total white blood cell counts was significantly lower in the HBV naïve, one month post treatment and three-month post treatment when compared with the control group. The levels of haemoglobin, packed cell volume, mean cell volume, mean cell haemoglobin and mean cell haemoglobin concentration were significantly lower in the HBV naïve, three months on treatment and six-months on treatment when compared with the control group (P<.05). Conclusion: In conclusion, it is possible that HBV infection has effect on iron metabolism and production of haematological precursor cells which are reflected in low levels of haemoglobin, PCV, MCV, MCH and MCHC as such these parameters could be used as co – markers to viral load in monitoring the treatment outcome of HBV infection in Nigeria.