Background: Phagocytosis is regarded to be impaired in HIV-1 infected adults, leading to high frequency and severity of several infections in this population. Data is contradictory with regards to individual facets in HIV infection.Objective: Aim of this study was to assess the phagocytic activity during the natural course of HIV infection. Method: It is a longitudinal study assessing natural course and impairment of neutrophil and monocyte phagocytosis in both naïve and HAART treated patients. Results: A lower neutrophil phagocytic activity was recorded in naïve patients compared to treated patients. Interestingly, a downward trend of neutrophil phagocytic activity was recorded in both groups, irrespectively of HAART intake, within 48 weeks of observation. Conclusion: Defects of innate immunity appear to be present in HIV infected patients regarding phagocytic activity of monocytes and of neutrophils which seems to decline over time. These deficiencies are influenced by the levels of CD4 cell counts and viral load.