Up to 70% of patients with systemic lupus erythematosus (SLE) are afflicted with neurologic manifestations. However, there are only a few reports documenting acute leukoencephalopathy in SLE. We describe a 20-year-old woman who was recently diagnosed as SLE, suffering from headache, fever and arthritis. She developed an acute onset of consciousness disturbance with seizure followed by prolonged coma, which recovered completely after 1 month of steroid therapy. Her brain MRI showed diffuse high signal intensity in the periventricular and subcortical white matter on T2-weighted and FLAIR images, whereas cerebral cortex, basal ganglia, and thalamus were spared. Acute leukoencephalopathy may be recognized as a subtype of lupus involving the central nervous system.