Neurocognitive outcome is an essential aspect of treatment for HIV-infected children. This study is aimed at assessing cognitive functioning in school-aged HIV-infected children and the change after receiving antiretroviral therapy (ART). We conducted a prospective cohort study of HIV-infected Thai children from 6-12 years of age compared with HIV-affected (children of HIV-positive mothers who were not infected with HIV), and normal control groups. Wechsler Intelligence Scale for Children-III (WISC-III) was administered at enrollment and 30 months of follow-up. Semistructured interviews of primary caregivers were performed. From April to October 2003, 121 children were enrolled; 39 HIV-infected, 40 HIV-affected, and 42 control children with a median age of 9.3 years. The HIV-infected group had a mean (standard deviation [SD]) CD4 percentage of 13.8% (5.3), 87% of whom had been receiving ART for a median of 35 weeks. At the first cognitive assessment, the mean (SD) of full-scale intelligence quotient (FSIQ) was 79 (13) and 88 (10) among HIV-infected and HIV-affected children, which was statistically lower than that of the control group at 96 (13; p < 0.01). The proportion of children with average intelligence level (FSIQ > 90) among 3 groups were 21%, 49%, and 76%, respectively (p < 0.01). At 30 months of follow-up, the HIV-infected group had a mean (SD) CD4 percentage of 25.6% (5.6); 77% had undetectable viral load. The mean (SD) FSIQ of children among three groups were 75 (12), 85 (12), and 91 (12), respectively. Compared with the baseline assessment, the verbal scale score significantly decreased in all groups, including the controls, whereas the performance scales did not change. In conclusion, school-aged HIV-infected children have lower cognitive function than HIV-affected and normal children. Cognitive function was not improved after receiving ART. Further study to address whether early ART can preserve cognitive functioning among HIV-infected children should be explored.