Background: The role of immune response to chronic hepatitis B virus (HBV) infection is complex; and the specific T-cell response to this infection can determine the duration and the extent of liver disease. Objective: This study aimed at assessing the profile of T-lymphocyte subpopulations in chronic hepatitis B (CHB) patients and its association with HBV replication. Methodology: The case group included 50 CHB patients with normal liver function tests (LFTs); and the control group included 50 age and sex-matched healthy individuals. The HBV markers, LFTs and serum viral load were measured in cases. Blood CD4 and CD8 T-lymphocyte subpopulations and the CD4/CD8 ratio were assessed in both groups by flow cytometry. Results: Our results showed significantly higher CD8 T-cells; significantly lower CD3 and CD4 T-cells; markedly reduced CD4/CD8 ratio in the cases as compared to the controls (P<0.001, for all). This T-cell impairment was also significantly linked to HBeAg positivity and elevated level of viraemia. The increased level of CD8 T-cells was significantly linked to both the HBeAg positivity (P<0.001) and the elevated level of viraemia (P=0.005), whereas the decreased levels of CD3, CD4 T-cells and CD4/CD8 ratio were significantly linked to both HBeAg positivity (P<0.001, in all) and the elevated level of viraemia (P<0.001, P=0.001& P=0.007, respectively). Conclusion: T-lymphocyte subpopulations imbalance could be expected by measuring the serum HBVeAg and the viraemia level in CHB patients exhibiting normal LFTs. These parameters are recommended to be measured regularly for the cellular immune function assessment.