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Background and Purpose: The pathophysiology of neurologic manifestations of postacute sequelae of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection is not clearly understood. Our aim was to investigate brain metabolic activity on [ 18 F] FDG-PET/CT scans in patients with a history of coronavirus disease 2019 (COVID-19) infection before imaging., Materials and Methods: This retrospective study included 45 patients who underwent [ 18 F] FDG-PET/CT imaging for any reason and had, at least once, tested positive for COVID-19 at any time before imaging. Fifteen patients had available [ 18 F] FDG-PET scans obtained under identical conditions before the infection. A group of 52 patients with melanoma or multiple myeloma who underwent [ 18 F] FDG-PET/CT were used as controls. Whole-brain 2-sample t test analysis was performed using SPM software to identify clusters of hypo- and hypermetabolism and compare brain metabolic activity between patients with COVID-19 and controls. Paired sample t test comparison was also performed for 15 patients, and correlations between metabolic values of clusters and clinical data were measured., Results: Compared with the control group, patients with a history of COVID-19 infection exhibited focal areas of hypometabolism in the bilateral frontal, parietal, occipital, and posterior temporal lobes and cerebellum ( P = .05 uncorrected at the voxel level, family-wise error-corrected at the cluster level) that peaked during the first 2 months, improved to near-complete recovery around 6 months, and disappeared at 12 months. Hypermetabolism involving the brainstem, cerebellum, limbic structures, frontal cortex, and periventricular white matter was observed only at 2-6 months after infection. Older age, neurologic symptoms, and worse disease severity scores positively correlated with the metabolic changes., Conclusions: This study demonstrates a profile of time-dependent brain PET hypo- and hypermetabolism in patients with confirmed SARS-CoV-2 infection., (© 2023 by American Journal of Neuroradiology.)