Introduction: Patients with systemic lupus erythematosus (SLE) are vulnerable to depression because of the chronic nature and neuropsychiatric involvement of the disease. Serum brain-derived neurotrophic factor (BDNF) was reported to be decreased in depression. The aim of the study was to investigate the prevalence of depression and its related factors including BDNF in patients with SLE. Material and Methods: One hundred and eighty patients were enrolled at the Rheumatology Clinic from January to March in 2012. The prevalence of depression was assessed using the center for epidemiologic studies depression (CES-D) scale. We evaluated disease activity by physician`s global assessment (PhyGA), patient`s global assessment (PGA), SLE disease activity index (SLEDAI) and disease related organ damage. The EuroQol-5 dimensions (EQ-5D), sociodemographic features and laboratory tests were also surveyed. Serum BDNF was measured using enzyme-linked immunosorbent assay (ELISA). Patients having a CES-D score of 24 or more were considered to have depression. Results: The prevalence of depression in SLE was 22.8% (n=41). In univariate analysis, unmarried/disrupted marital status (patients with single/divorced/estrangement/bereavement status than those with married status), unemployment, low annual income, higher PGA, higher PhyGA, lower EQ-5D index score and severe pain/discomfort were significantly associated with depression. In multivariate analysis, unmarried/disrupted marital status, higher PGA and severe pain/discomfort were significantly associated with depression. Serum BDNF levels were not associated with depression (p=0.62) but negatively correlated with disease activity in patients with SLE (r=-0.188, p=0.021). Conclusion: Depression is prevalent in patients with SLE and is associated with unmarried/disrupted marital status, severe pain/discomfort and higher PGA. Serum levels of BDNF were not associated with depression but were negatively correlated with disease activity. Treatment of depression may be beneficial in patients with severe pain/discomfort or high PGA.