Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect various organs, including the central nervous system (CNS), leading to neuropsychiatric manifestations known as neuropsychiatric systemic lupus erythematosus (NPSLE). NPSLE can present with cognitive dysfunction, organic brain syndromes, delirium, seizures, headache, and psychosis. The pathogenesis of NPSLE involves multiple factors, including genetic predispositions, autoantibodies, cytokines, and immune complexes. Autoantibodies such as anti-dsDNA, anti-SS(A), anti-SS(B), anti-Smith, and anti-neuronal DNA are characteristic features of SLE. The diagnosis of NPSLE is challenging due to the lack of specific biomarkers, and treatment options are primarily symptomatic, including antipsychotics, antidepressants, anxiolytics, antiepileptics, and immunosuppressants. The management of NPSLE aims to provide symptomatic relief and address the underlying SLE process, which can be inflammatory, non-inflammatory, or thrombotic. The article also discusses the role of specific autoantibodies, such as anti-ribosomal P, anti-NMDA receptor, and anti-MAP-2, in the pathogenesis of NPSLE. Additionally, it highlights the importance of biomarkers in improving diagnostic efficiency and the potential complications of NPSLE, such as steroid-induced psychosis and progressive multifocal leukoencephalopathy (PML).Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect various organs, including the central nervous system (CNS), leading to neuropsychiatric manifestations known as neuropsychiatric systemic lupus erythematosus (NPSLE). NPSLE can present with cognitive dysfunction, organic brain syndromes, delirium, seizures, headache, and psychosis. The pathogenesis of NPSLE involves multiple factors, including genetic predispositions, autoantibodies, cytokines, and immune complexes. Autoantibodies such as anti-dsDNA, anti-SS(A), anti-SS(B), anti-Smith, and anti-neuronal DNA are characteristic features of SLE. The diagnosis of NPSLE is challenging due to the lack of specific biomarkers, and treatment options are primarily symptomatic, including antipsychotics, antidepressants, anxiolytics, antiepileptics, and immunosuppressants. The management of NPSLE aims to provide symptomatic relief and address the underlying SLE process, which can be inflammatory, non-inflammatory, or thrombotic. The article also discusses the role of specific autoantibodies, such as anti-ribosomal P, anti-NMDA receptor, and anti-MAP-2, in the pathogenesis of NPSLE. Additionally, it highlights the importance of biomarkers in improving diagnostic efficiency and the potential complications of NPSLE, such as steroid-induced psychosis and progressive multifocal leukoencephalopathy (PML).