Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by abnormal production of autoantibodies and proinflammatory cytokines. Although interleukin-33 (IL-33), a novel number of the IL-1 family, has been reported to have proinflammatory effects, the association of IL-33 with SLE has remained unknown. The aim of this study was to examine whether the serum IL-33 level is associated with SLE. A total of 70 patients with SLE were recruited. Sera from these patients were obtained at their visit and were compared to sera from 40 healthy controls or 28 patients with rheumatoid arthritis (RA) for IL-33 level. Furthermore, blood samples from patients with SLE were determined for various SLE-related laboratory variables, including blood routine, complements, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and some autoantibodies. Serum IL-33 level was significantly increased in patients with SLE, compared with healthy controls, but was lower than that with RA. In patients with SLE, most clinical and laboratory characteristics did not correlate with serum IL-33 levels, with exceptions of thrombocytopenia, erythrocytopenia, anti-SSB antibody, ESR, CRP and IgA. By Spearman's correlation coefficient, patients with SLE showed close correlation of IL-33 with ESR, CRP and IgA, and by multivariate logistic regressions, patients with SLE showed significantly independent association of IL-33 with thrombocytopenia, erythrocytopenia and anti-SSB antibody. Our results suggest that IL-33 may play a role in acute phase of SLE, but it was not associated with course of the disease. Moreover, IL-33 may exert biologic effects on erythrocytes and platelets or their precursors in SLE.