Human immunodeficiency virus (HIV)-related dementia is the most severe form of neurocognitive disorder in patients with AIDS. It is relatively uncommon in postantiretroviral therapy (HAART) era and is associated with a high cerebrospinal fluid CSF/plasma viral load. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has proven useful in malignancies, infections, and central nervous system lesions in HIV-infected patients and has been used to explore regional cerebral glucose metabolism patterns in HIV-positive patients with and without cognitive impairment. We present the case of a 36-year-old male with AIDS presenting as pyrexia of unknown origin, where global brain hypometabolism was noted incidentally on FDG PET/CT referred for identification of the infective focus/tumor causing the fever.