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Neuropsychiatric systemic lupus erythematosus (NPSLE) affects the brain, spinal cord, or other nerves and leads to neurological and psychiatric symptoms directly related to SLE. We report a series of four female patients with NPSLE as the first presentation for SLE. None of them were previously diagnosed with SLE. The first case involved a 50-yearold patient who presented with back pain and lower limb weakness for three weeks associated with numbness. A lumbar puncture was done, and CSF analysis showed high WBC and normal glucose levels with negative CSF cultures for bacteria. The patient was diagnosed with aseptic meningitis and treated with antibiotics and antiviral medication without improvement. So she was treated as a case of SLE aseptic meningitis with steroids. In the second case, a 20-yearold patient had a generalized tonic-clonic seizure with the acute manifestation of hypertensive urgency. Magnetic resonance imaging (MRI) was done and suggested posterior reversible encephalopathy syndrome (PRES). The third case was for a 38-year-old patient who complained of dizziness, general weakness, and convulsion. On review of the systems, the patients had positive symptoms of SLE. Anti-nuclear antibody (ANA) and double-stranded ds-DNA were positive. Computed tomography (CT) scans were done and showed a thymoma. The patient was diagnosed with SLE in association with focal seizures and thymoma. In the last case, a 44-year-old patient presented with tongue heaviness and right-side weakness. MRI revealed small acute lacunar infarction scattered at both cerebral hemispheres and the right side of the cerebellum, and chest CT showed pulmonary embolism (PE). The patient was diagnosed with an acute ischemic stroke and PE related to SLE. In conclusion, the neurological manifestations of SLE are a significant issue for both patients and clinicians. Here we report a unique case series and describe the prognosis and outcome of the treatment in these cases.