Many patients with systemic lupus erythematosus have central nervous system involvement. Routine diagnostic studies may not yield evidence of neuropsychiatric dysfunction and are therefore not useful as objective measures to monitor treatment response. We present a case of a 64-year-old woman whom we diagnosed with systemic lupus erythematosus by the American College of Rheumatology criteria after she reported recent cognitive decline. Neuropsychological assessment showed prominent deficits, and an F-18 fluorodeoxyglucose positron emission tomography scan of the brain showed significant abnormalities. Both the neuropsychiatric and scan abnormalities improved dramatically with immunosuppressive treatment. F-18 fluorodeoxyglucose positron emission tomography shows promise in the diagnosis and treatment monitoring of patients who have lupus with neuropsychiatric involvement.