The aim of this study was to study the neuropsychiatric (NP) manifestations, diagnostic evaluation, treatment and outcome in juvenile systemic lupus erythematosus (SLE). We reviewed the charts of all children with SLE and evidence of NP manifestations as defined by the presence of at least one of the following: headache, cerebrovascular accident (CVA), chorea, seizure, papilledema, and psychiatric or spinal cord manifestations. Out of 90 children with SLE, 20 (16 female) had NP manifestations. The mean age at onset was 8.8 years. The mean period between onset of SLE and NP manifestations was 10.2 months. NP manifestations were the presenting feature in 3 patients. Eleven patients had headache, 10 had psychiatric manifestations, 10 had seizure and 6 had CVA. Coma was seen in 5 patients, chorea in 4, transverse myelitis in 2 and papilledema in 2. Anticardolipin antibodies were high in 12 patients. Five patients had an abnormal CSF study. Nine patients had EEG abnormalities and 13 showed MRI abnormalities. All patients received oral prednisone and 17 were treated with IVMP and immunosuppressive therapy (cyclophosphamide or azathioprine); 85% of our patients recovered completely, but 15% had persistent NP sequelae; 10% died from severe infection. In conclusion, NP involvement in juvenile SLE is common. However, early diagnosis and early treatment with adjunctive intravenous pulse cyclophosphamide may improve the outcome.