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Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disorder characterized by a wide range of immunological abnormalities. One of its notable features is the potential to affect the central nervous system (CNS), leading to diverse neurological manifestations including headaches, acute state of confusion, seizure disorder, cerebrovascular disease, and meningoencephalitis. CNS involvement is highly prevalent in SLE patients, ranging from 12% to 75%, and is associated with a poor prognosis. Treatment options such as steroids, azathioprine, rituximab, and intravenous immunoglobulins (IVIGs) have been considered in managing these cases. However, early diagnosis of SLE-related CNS involvement remains challenging due to the rapid progression of symptoms and the need to exclude various alternative di-agnoses. In this article, we present a fatal case of an SLE patient with meningoencephalitis, initially resembling an ischemic stroke. Despite administering antibiotics, antiviral agents, IVIGs, steroids, rituximab, and plasma exchange, no clinical improvement was observed.