T cell activation plays an important role in driving CD4 depletion during the course of HIV infection. There is scarce information about activation of different T cell subsets in HIV(+) individuals experiencing distinct disease progression. The activation of different CD4(+) and CD8(+) T cell subsets and its contribution to total T cell activation were examined measuring CD38 expression by flow cytometry in 120 HIV-infected individuals and 9 uninfected healthy controls. HIV-infected patients were divided into four groups: 11 elite controllers (EC), 14 viremic controllers (VC), 61 antiretroviral-naive typical progressors (TP), and 34 progressors with viral suppression (VS) under antiretroviral therapy. EC displayed significantly greater activation levels than VS, with a higher contribution of central memory subsets to the activation of total CD8 T cells (p = 0.002). The activation of central memory CD8(+) T cells significantly correlated with viral load in TP regardless of CD4 counts. In contrast with VS, proviral load was undetectable in all EC. Compared to VS, EC display abnormal and higher activation levels of different CD8(+) T cell subsets. Factors other than the size of the viral reservoir should explain the high level of activation of central memory CD8(+) T cells characteristically seen in HIV(+) individuals with spontaneous control of viral replication.