Background: Neuropsychiatric systemic lupus erythematosus (NPSLE) has a diverse and broad spectrum of severity and prognosis, with some devastating manifestations. However, its diagnosis and treatment remain unclear and controversial. Case Report: A 19-year-old woman with SLE presented with fever, headache, quadriparesis, and tremor. Brain magnetic resonance imaging (MRI) showed sulcal enhancement in the cortical sulcus, and intravenous methylprednisolone (500 mg/day) and immunoglobulin (2 g/kg for 5 days) were started under the suspicion of aseptic lupus meningitis. However, the patient’s neurologic symptoms worsened; brain MRI showed a newly developed brain parenchymal lesion, suggesting lupus cerebritis and posterior reversible encephalopathy syndrome. Two cycles of rituximab (850 mg/day, 1-week interval) were administered for the treatment of refractory NPSLE. Her neurologic symptoms gradually improved after the second cycle, and she was discharged with minimal neurologic symptoms. Conclusion: Rituximab may be a therapeutic option for refractory lupus cerebritis. Further research is needed to accurately determine its efficacy.