Background: Serum β2 microglobulin, a low molecular weight polypeptide chain, is present in all nucleated cells in the body. Serum levels are elevated in viral infections including Human Immunodeficiency Virus (HIV) and haematological malignancies. Elevated serum β2 microglobulin levels have been shown to be a good predictor of disease progression in HIV infection. The burden of monitoring disease progression in HIV infection is enormous in developing countries like Nigeria. A surrogate marker like β2 microglobulin will be valuable in monitoring HIV infection. Objective: The objective of this study was to determine the serum levels of β2 microglobulin in HIV infected patients and evaluate its utility as a measure of disease activity and severity. Materials and Methods: A cross-sectional study comprising eighty (80) HIV seropositive subjects and thirty (30) HIV seronegative controls. Serum β2 microglobulin levels were assayed with enzyme linked immunosorbent assay (ELISA) test kits by Teco Diagnostics, Anaheim, CA, USA. Data was analysed using SPSS version 16. Results: The mean β2 microglobulin levels among HIV seropositive subjects and controls were found to be 4.36mg/L and 2.28mg/L respectively (P<0.001). The mean β2 microglobulin levels among HAART and HAART naïve patients were 4.20mg/L and 4.53mg/L respectively (P=0.226). The mean serum β2 microglobulin levels in asymptomatic and symptomatic subjects were 4.17mg/L and 5.75mg/L respectively (p<0.001). There was a negative correlation between serum β2 microglobulin and total lymphocyte counts(r=-0.350; P=0.001), serum β2 microglobulin and CD4+ lymphocyte counts(r=-0.700; P<0.001). Conclusion: Serum β2 microglobulin level is a useful prognostic indicator for disease activity and severity in HIV infection. It can be used as a surrogate marker to CD4+ lymphocyte counts in HIV infected patients.