We aimed to evaluate the brain hypometabolic signature of persistent isolated olfactory dysfunction after SARS-CoV-2 infection. Twenty-two patients underwent whole-body [18F]-FDG PET, including a dedicated brain acquisition at our institution between May and December 2020 following their recovery after SARS-Cov2 infection. Fourteen of these patients presented isolated persistent hyposmia (smell diskettes olfaction test was used). A voxel-wise analysis (using Statistical Parametric Mapping software version 8 (SPM8)) was performed to identify brain regions of relative hypometabolism in patients with hyposmia with respect to controls. Structural connectivity of these regions was assessed (BCB toolkit). Relative hypometabolism was demonstrated in bilateral parahippocampal and fusiform gyri and in left insula in patients with respect to controls. Structural connectivity maps highlighted the involvement of bilateral longitudinal fasciculi. This study provides evidence of cortical hypometabolism in patients with isolated persistent hyposmia after SARS-Cov2 infection. [18F]-FDG PET may play a role in the identification of long-term brain functional sequelae of COVID-19.