© 2016 Iqbal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Purpose To measure cerebral metabolite levels in perinatally HIV-infected youths and healthy controls using the accelerated five dimensional (5D) echo planar J-resolved spectroscopic imaging (EP-JRESI) sequence, which is capable of obtaining two dimensional (2D) J-resolved spectra from three spatial dimensions (3D). Materials and Methods After acquisition and reconstruction of the 5D EP-JRESI data, T1 -weighted MRIs were used to classify brain regions of interest for HIV patients and healthy controls: right frontal white (FW), medial frontal gray (FG), right basal ganglia (BG), right occipital white (OW), and medial occipital gray (OG). From these locations, respective J-resolved and TE-averaged spectra were extracted and fit using two different quantitation methods. The J-resolved spectra were fit using prior knowledge fitting (ProFit) while the TE-averaged spectra were fit using the advanced method for accurate robust and efficient spectral fitting (AMARES). Results Quantitation of the 5D EP-JRESI data using the ProFit algorithm yielded significant metabolic differences in two spatial locations of the perinatally HIV-infected youths compared to controls: elevated NAA/(Cr+Ch) in the FW and elevated Asp/(Cr+Ch) in the BG. Using the TE-averaged data quantified by AMARES, an increase of Glu/(Cr+Ch) was shown in the FW region. A strong negative correlation (r < -0.6) was shown between tCh/(Cr+Ch) quantified using ProFit in the FW and CD4 counts. Also, strong positive correlations (r > 0.6) were shown between Asp/(Cr+Ch) and CD4 counts in the FG and BG. Conclusion The complimentary results using ProFit fitting of J-resolved spectra and AMARES fitting of TE-averaged spectra, which are a subset of the 5D EP-JRESI acquisition, demonstrate an abnormal energy metabolism in the brains of perinatally HIV-infected youths. This may be a result of the HIV pathology and long-term combinational anti-retroviral therapy (cART). Further studies of larger perinatally HIV-infected cohorts are necessary to confirm these findings.