We evaluated the functional brain changes in HIV-infected children by mapping the amplitude-of-low-frequency-fluctuations (ALFF) and functional connectivity (FC) using rs-fMRI. Association of these changes with cognitive measures was also explored. ALFF and FC were significantly altered in multiple brain regions involved in auditory, visual, language, motor and sensory activity. The waning cognitive functions in HIV-infected children were associated with the changes in ALFF and FC. These two imaging parameters in association with the cognitive evaluation may provide better understanding of the functional brain activity in HIV-infected children.