Africans have elevated T cell activation compared to residents of Europe or the USA. Levels of T cell activation also correlate with disease progression in HIV-infected individuals. We sought to determine if treatment with antiretroviral therapy (ART) would reduce levels of T cell activation (CD38 and HLADR co-expression) in HIV-infected Ugandan children. The median CD8+ T cell activation level among 199 ART-treated children (30%) was lower than in 57 ART-naïve children (45%, p<0.001), but remained higher than in 30 HIV-uninfected children (18%, p<0.001). Among ART-treated children, CD4% was inversely correlated with both CD8- (rho=-0.61, p<0.001) and CD8+ (rho=-0.38, p<0.001) T cell activation. Prospectively, CD4 recovery correlated with post-treatment CD8+ T cell activation level (p=0.008). Our data suggest that significant decreases in T cell activation accompany CD4 recovery in ART-treated HIV-infected African children, to levels that approach but do not reach those of uninfected children.