It has been hypothesized that hypothalamus is involved in narcolepsy. The relative difference between cerebral glucose metabolism of 24 narcoleptic patients and 24 normal controls was studied using 18F-fluorodeoxy glucose positron emission tomography. Patients with narcolepsy showed significantly reduced cerebral glucose metabolism in bilateral rectal and subcallosal gyri, the medial convexity of right superior frontal gyrus, bilateral precuneus, right inferior parietal lobule, and in left supramarginal gyrus (uncorrected p < 0.001). Bilateral posterior hypothalami and mediodorsal thalamic nuclei showed hypometabolism with significance at the level of corrected p < 0.05, with small volume correction. This study showed cerebral glucose hypometabolism of the hypothalamus-thalamus-orbitofrontal pathways in the narcoleptic brain.