T helper 17 (TH17) cells are beginning to be implicated in the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that interleukin 27 (IL-27) controls the development of TH17. However, whether IL-27 plays a role in the development of SLE is still unclear. In the present work, we investigated the serum IL-27 level in SLE and its relations to disease activity. Fifty-six patients with SLE and 30 healthy volunteers were recruited. Serum IL-27 levels were detected by enzyme-linked immunosorbent assay. The clinical and laboratory parameters were collected from medical records or by questionnaire. The serum IL-27 level in SLE patients was significantly lower than that in healthy controls (P < 0.001). Compared with SLE patients without nephritis, patients with nephritis had a significantly decreased serum IL-27 level (P < 0.05). However, there was no significant difference between less active and more active SLE (P > 0.05). Correlation analysis between serum IL-27 levels and SLE disease activity index showed no association (P > 0.05). In summary, a decrease in serum IL-27 level in patients with SLE suggested that this cytokine might be implicated in the pathomechanism of this disease.