Background: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are currently two important blood-borne human pathogens of major public health concern with high prevalence rates in Africa. Objectives: The study assessed the impact of HIV and HBV mono- and co-infections on serum total protein, albumin, globulin fractions and plasma free amino acids concentrations. Methods: This was a cross-sectional study on adult (25 – 64 years old) patients on Highly Active Antiretroviral Therapy attending AIDS Preventive Initiative in Nigeria Centre, Jos University Teaching Hospital, Plateau State, Nigeria. It involved 80 subjects; 20 HIV/HBV co-infected, 20 each of HIV and HBV mono-infected controls, and 20 seronegative controls. Results: Significant (p<0.05) increases in total protein and gamma globulin but a reduction in albumin concentrations were observed in the HIV/HBV co-infected group. Similarly, significant (p<0.05) increases in alpha-1 and alpha-2 globulin concentrations were observed in the mono- and co-infected groups compared to the seronegative control group. There were significant (p<0.05) increases in the glucogenic, aromatic and branched-chain amino acid concentrations of the HIV/HBV co-infected subjects. Conclusion: The study suggests prognostic importance of alpha and gamma globulin fractions of serum protein as well as amino acid profile in the management of HIV/HBV co-infection. Keywords: Total protein; albumin; globulin; amino acid; viral infection.