Objectives: To investigate the impact of early combined antiretroviral therapy (cART) on infammation biomarkers and immune activation during acute and early chronic HIV-1 infection. Methods: We included 12 acute (AHI), 11 early chronic (EcHI), and 18 late chronic HIV-1-infected (LcHI) individuals who were treated with cART and 18 HIV-1-uninfected (HIV-neg) individuals. Plasmatic levels of infammation biomarkers, CD8+CD38+HLA-DR+ T cell frequencies, CD4 T cell counts, CD4/CD8 ratio, total HIV-1 DNA and plasmatic viral load were evaluated. Mann–Whitney test, Pearson and Spearman correlation, and linear regression models were used for statistical analyses. Results: IP-10, IL-18, and sCD163 were signifcantly elevated at pre-ART in the AHI and EcHI groups, showing a signifcant reduction after 6 months of cART in the AHI group, achieving similar levels to the HIV-neg group. For the EcHI group, the IP-10 and sCD163 levels were also signifcantly reduced on M6-ART; however, IP-10 levels remained higher than in the HIV-neg group, and no signifcant reduction of IL-18 levels was observed. The CD8+ T cell activation levels were elevated in the AHI and EcHI groups at pre-ART and showed a signifcant reduction on M6-ART, but they were similar to levels seen for HIV-neg only after 12 months of cART. At pre-ART, IP-10 levels but not IL-18 levels were positively correlated with HIV-1 viral load in the AHI group. Conclusions: Early initiation of cART in HIV infection can reduce systemic infammation, but the earlier normalization of the infammation markers was only observed when cART was initiated in the acute phase of infection. A slower dynamic of reduction was observed for CD8+ T cell activation.