Background: Hepatitis B virus (HBV) infection remains a major public health challenge in sub-Saharan Africa, including Nigeria. In addition to hepatic damage, HBV disrupts haematopoiesis, iron metabolism, and immune regulation, resulting in altered haematological and inflammatory profiles. Understanding these changes may improve disease monitoring and patient management. Objective: This study evaluated the serological status of HBV and the associated variations in haematological parameters, serum ferritin, and interleukin-6 (IL-6) among individuals in Abakaliki metropolis, Ebonyi State, Nigeria. Methods: A descriptive cross-sectional study was conducted among 1,000 adults recruited from selected healthcare facilities in Abakaliki. Venous blood samples (6 mL) were collected and separated into EDTA and plain tubes for haematological and biochemical analyses. HBV screening was carried out using a rapid diagnostic test, and serological markers were determined using ELISA. Haematological parameters were analysed using an automated analyzer, while ferritin and IL-6 were measured using ELISA and fluorescence immunoassay methods, respectively. Statistical analysis was performed at a significance level of p < 0.05. Results: Active HBV infection occurred in 7.5% of participants, while 30.8% had inactive infection, 27.5% were vaccinated, and 16.7% were uninfected. Significant variations were observed in RBC, Hb, PCV, MCV, MCH, MCHC, RDW, TWBC, and platelet count across the groups (p < 0.05). The active infection group showed the lowest RBC and platelet counts but the highest TWBC and IL-6 levels. Ferritin was lowest in active cases and highest in vaccinated individuals. Gender analysis revealed similar trends in males and females, though lymphocyte and monocyte counts were significantly higher in males with active infection. Conclusion: HBV infection significantly alters haematological indices and inflammatory markers, particularly in individuals with active disease. Routine m