This study evaluated the salivary concentrations of lactoferrin (Lf) in HIV-seropositive and -seronegative subjects correlating these levels with the incidence of periodontal disease, quantity of Candida spp and systemic condition of the HIV-seropositives (viral load and T lymphocytes CD-4+ count and antiretroviral therapy). Whole saliva samples were obtained from 109 subjects who were divided into four groups according to the extent of their HIV infection and their periodontal condition. The salivary Lf concentrations were determined by a standard enzyme-linked immunosorbent assay and the quantification of Candida spp. was obtained from all subjects. Among the HIV- participants, higher concentrations of Lf were found in individuals with periodontal diseases (p<0.0001). A similar result was found for HIV+ participants (p<0.0001). No correlation was found between the concentration of salivary Lf and the quantification of Candida spp or between the Lf concentration and the systemic condition of the HIV+ subjects. The existence of periodontal diseases can modulate an early inflammatory process in the oral mucosa by increasing the expression of Lf, where Lf can act as an antibacterial peptide in HIV- and HIV+ patients. These results suggest that Lf is a possible marker for periodontal diseases in immunocompetent and immunocompromised subjects.