There are no positron emission tomography (PET) studies reported in the literature with regards to brain metabolism and function in patients with Lyme disease. These patients frequently present with various neurological symptoms, including memory problems. We used [(18)F]fluorodeoxyglucose (FDG) PET to determine the metabolic landscape in 23 patients with Lyme disease. Images were evaluated for cortical and subcortical abnormalities by two experienced reviewers blinded to the clinical information. The most striking finding was hypometabolism in the temporal lobes in 17/23 (74%) patients. Of these, 12 had bilateral temporal lobe hypometabolism, two had left temporal lobe, and three had right temporal lobe hypometabolism. Seven of the patients with temporal lobe hypometabolism had diffuse cortical hypometabolism that included the frontal and parietal lobes. Lyme disease appears to have two primary patterns of brain involvement on FDG PET scans, specific temporal lobe hypometabolism or a diffuse cortical hypometabolism. The involvement of the temporal lobes in both patterns is likely associated with the memory disturbances described in many of these patients. Although there was no clear diagnostic pattern, and many of the defects were mild, FDG PET imaging may provide important information regarding the areas of the brain affected in patients with neurological symptoms associated with Lyme disease.