Twenty children older than 2 y infected with human immunodeficiency virus (HIV) were examined by in vivo proton magnetic resonance spectroscopy (1H MRS) to study their cerebral metabolism and to identify metabolic profiles in relation with different stages of the disease. Patients were rated regarding their clinical and immunologic status according to the Centers for Disease Control classification and were divided into two groups: without encephalopathy (E-, n = 15) and with progressive encephalopathy (E+, n = 5). The acquisition was performed in the centrum semiovale using the short echo stimulated echo acquisition mode 20-ms sequence. The MRS profile was abnormal in all HIV-infected children compared with healthy age-matched controls (n = 7), even when magnetic resonance images were normal. A significant increase of the proportion of the lipid signals (ANOVA, p < 0.05) was found in all HIV-infected children. In addition, a significant decrease of the proportion of the N-acetylaspartate signal and a significant increase of the proportion of the myo-inositol signal (ANOVA, p < 0.05) characterized the E+ group. The principal component analysis performed on eight variables on 30 spectra confirms that the spectra of HIV-infected children differ from control spectra. The E+ group and the E- group are clearly separated on the map of subjects on the principal plane. The E- group lies in an intermediate position between the E+ group and the control group. The evolution of metabolic alterations in the brain of HIV-infected children can clearly be monitored by 1H MRS and associated with the occurrence of an encephalopathy.