Persistent immune actiation is associated with innadequate immune recovery in HIV-patients. This study assessed the relationship between frequency of expression of cell activation markers (CD38 and HLADR) and presence of oral lesions in HIV-1 infected patients. Fifty-seven HIV-infected persons, undergoing antiretroviral treatment, were divided into three groups, according to the number of CD4 T cells and CD4 /CD8 ratio: adequate, partial, and inadequate immune restauration. All patients underwent full mouth assessments for saliva flow measurement, oral mucosal lesion, periodontal disease, and severity of periodontitis. Immune activation markers levels were compared according to three groups of periodontal disease ("No periodontal disease," "gingivitis," and "periodontitis"). Oral mucosal lesions (P = 0.03) and peridodontal disease (P = 0.03) were associated with lower CD4 /CD8 ratio. Patients with oral mucosal lesions had significantly higher median levels of HLADR and CD38 markers in all T-lymphocytes populations than patients without oral lesions. Patients with gingivitis and with periodontitis presented significantly higher median levels of CD3 HLADR , CD4 HLADR , CD8 HLADR , and CD3 CD38 and significantly lower CD4 /CD8 ratio than patients with no periodontal disease. Increased levels of HLADR and CD38 expressions in peripheral blood were associated with oral lesions in HIV-positive patients. Periodontal disease was associated with HLADR expression.