In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs. Measurements of cerebral blood flow and metabolism by means of positron emission tomography (PET) and single-photon emission tomography (SPET) can contribute to the diagnostic assessment of the involvement of the central nervous system (CNS) in SLE. Functional imaging has been proven to be more sensitive than morphological imaging (magnetic resonance imaging and computed tomography). In this report, we present the case of a 70-year-old female patient, suffering from SLE without symptoms of CNS involvement. In addition to a SPET study using technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) and a PET scan with fluorine-18 deoxyglucose (18FDG), a SPET study after acetazolamide injection was performed in order to assess the cerebral perfusion reserve. While the PET scan showed no major abnormalities, and the baseline SPET study revealed only minor changes, the acetazolamide-enhanced SPET study revealed a marked reduction of the cortical perfusion reserve, particularly in both frontal lobes. It is concluded that "preclinical" CNS involvement, mainly caused by pathological mechanisms involving the cerebral blood vessels, can be considered to exist in this patient with SLE.