•Medial and inferior frontal lobe hypometabolism on FDG-PET was associated with high SUDEP risk in our cohort.•This pattern may serve as an imaging biomarker for those at increased risk of SUDEP.•Definite and probable SUDEP patients demonstrated a similar metabolic pattern on their individual PET scans.•Frontal lobe dysfunction may play a role in the pathophysiology of SUDEP, and FDG PET can be used to identify patients at high risk. Abnormalities of brain structures and neuronal networks have been identified in MRI studies of patients with Sudden Unexpected Death in Epilepsy (SUDEP) as well as in those at elevated risk. The goal of this study was to identify common patterns of objectively detected brain glucose metabolic abnormalities associated with SUDEP patients and those at high SUDEP risk. Patients with refractory epilepsy (n = 78, age: 16–61 years, 44 females), who underwent comprehensive presurgical evaluation, were assessed for their risk of SUDEP using the revised SUDEP-7 inventory. From the 57 patients with low SUDEP risk, 35 were selected to match their demographic and clinical characteristics to those with high SUDEP risk (n = 21). 18Ffluoro-deoxy-glucose positron emission tomography (FDG-PET) abnormalities were evaluated in the high- and low-SUDEP risk subgroups compared to FDG-PET scans of a healthy adult control group using statistical parametric mapping (SPM). Individual FDG-PET scans of 4 additional patients, who died from SUDEP, were also analyzed by SPM. Mean SUDEP-7 score was 6.1 in the high and 2.7 in the low SUDEP risk group. MRI showed no lesion in 36 patients (64%). Statistical parametric mapping analysis of the high SUDEP risk subgroup showed bilateral medial frontal and inferior frontal hypometabolism as a common pattern. The low-risk group showed no specific common metabolic abnormalities on SPM group analysis. Individual PET scans of all 4 patients who died from SUDEP also showed bilateral frontal lobe hypometabolism. These data show that bilateral frontal lobe involvement on FDG-PET, especially the medial and inferior frontal cortex, may be a common metabolic pattern associated with high SUDEP risk and SUDEP itself, in patients with refractory focal epilepsy.