Background The association between brain-derived neurotrophic factor (BDNF) and systemic lupus erythematosus (SLE) is controversial, and no study investigated the clinical associations of BDNF in patients with childhood onset systemic lupus erythematosus (cSLE). In this study, we aimed to investigate the serum levels of BDNF in patients with cSLE and examine whether a relationship of BDNF exists among depression, anxiety, and sleep quality. Methods Thirty patients and age-sex matched healthy controls were included. Depression, anxiety, sleep quality and quality of life were assessed by relevant questionnaires. Disease activity was assessed according to the SLE disease activity index (SLEDAI) and serum BDNF level was measured by the enzyme-linked immunosorbent assay method. Results Serum BDNF level was significantly lower in cSLE patients than healthy controls (21981 vs 29905 pg/mL, p = 0.001) and significantly decreased level was observed in active cSLE (SLEDAI >0), then those with SLEDAI = 0 (17110 vs 26852 pg/mL, p = 0.005). Although the scores of the depression, anxiety, sleep quality and quality of life questionnaires were strongly correlated with each other, no correlation was observed with serum BDNF levels. Conclusions In patients with cSLE, serum level of BDNF was significantly decreased compared to healthy controls. Our results suggest that serum BDNF levels were not associated with the presence of anxiety, depression and poor sleep quality and might be dictated by the pathophysiological process of SLE rather than mood disorders.