Objectives Brain-derived neurotrophic factor (BDNF) is an important mediator of neuronal development, survival, and function. It is related to the pathogenesis of several neuropsychiatric disorders. The aim of this study was to determine the relationship between serum BDNF (sBDNF) level and neuropsychiatric status in systemic lupus erythematosus (SLE) patients. Patients and methods This study included the following groups: group I included 35 SLE patients with neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations, group II included 30 SLE patients without neuropsychiatric manifestations, group III included 15 patients with neuropsychiatric disorders due to causes other than SLE, and group IV included 15 apparently healthy volunteers. All groups were matched for age and sex. SLE disease activity was assessed using the SLE Disease Activity Index. A Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Axis I was used for the assessment of psychiatric disorders, whereas neurological disorders were assessed by an expert neurologist. sBDNF was measured by the enzyme-linked immunosorbent assay. Results There was a statistically significant increase (P