Brain involvement in systemic lupus erythematosus (SLE) is a significant source of morbidity and mortality. Therefore, the early detection and treatment of brain involvement in SLE is of utmost importance; however, a confirmative diagnostic tool for neuropsychiatric SLE is yet to be developed. In this study, we investigated the efficacy of (18)F-FDG-PET for detection of brain involvement in patients with SLE with normal magnetic resonance imaging (MRI) findings. Twenty patients with SLE, who presented with neuropsychiatric symptoms despite normal brain MRI findings and who underwent brain (18)F-FDG-PET, were enrolled. The most common neuropsychiatric manifestation was headache (45%), followed by seizure (20%) and mood disorder (20%). (18)F-FDG-PET revealed significant glucose metabolic abnormalities in 15 of 20 patients (75%). The temporal (55%) and the occipital (55%) lobes were the most susceptible brain regions, followed by the frontal lobe (50%). However, neuropsychiatric symptoms were not geographically correlated to (18)F-FDG-PET findings. Two patients with abnormal (18)F-FDG-PET findings underwent follow-up brain (18)F-FDG-PET after remission, which showed complete resolution of abnormal glucose metabolism. Our data suggest that (18)F-FDG-PET may be an additional diagnostic modality complementary to MRI, when MRI is unable to provide evidence of brain involvement in patients with SLE.