Background: As life expectancy of HIV-infected patients increases with use of highly active antiretroviral therapy (HAART), protean haematologic manifestation including decreased activity of natural anticoagulants such as protein C may occur in the absence of genetic risk factors. Based on this preposition, we assessed the plasma level of protein C, and prevalence of factor V Leiden mutation among HIV-infected individuals. Our cohort consisted of 499 HIV-infected patients, of which 250 had AIDS, while 249 were either asymptomatic or had minor muco-cutaneous infection consistent with WHO clinical stages I and II without features of AIDS. We also evaluated 251 healthy, HIV-negative subjects as controls. All participants were tested for plasma protein C levels and factor V Leiden (FVL) mutation (Arg 506 Gln) by automation and amplification created restriction enzyme site (ACRES) polymerase chain reaction, respectively. The prevalence of reduced protein C plasma levels among HIV positive patients was 20%; it was more prevalent among those that had AIDS compared with those without features of AIDS, but within WHO clinical stage I and II, (93.3% vs 6.7%) respectively. None of the control patients had either reduced protein C nor FVL mutation. All participants that demonstrated reduced protein C plasma levels demonstrated normal FVL genotype (1691G/G). Conclusion: Decreased protein C plasma levels can occur in HIV-infected pa-* Corresponding author. S. O. Obi et al. 77 tients in the absence of factor V Leiden mutation. The risk increases with severity of the disease. Deranged protein C plasma level increases the risk of hypercoagulable state in patients with advanced HIV disease; it should be considered among the causes of thrombo embolism in this group of patients.