Objective To investigate the value of tumor necrosis factor receptor 2 (TNFR2) in assessing disease activity in systemic lupus erythematosus (SLE). Methods Fifty-four SLE patients and 28 healthy controls were recruited from our institution from January 2020 to March 2022. Serum levels of interleukin (IL)-6, IL-10, interleukin-1 receptor antagonist (IL-1RA) and TNFR2 were measured using enzyme-linked immunosorbent assay kits. The value of these cytokines in diagnosing SLE and distinguishing active from inactive SLE was assessed using receiver operating characteristic (ROC) curves.Results Serum levels of IL-6, IL-10, IL-1RA and TNFR2 were significantly higher in SLE patients compared to healthy controls (P＜0.05). There was a significant positive correlation between SLEDAI-2K scores and IL-10 (r=0.338, P=0.015), IL-1RA (r=0.385, P=0.005) and TNFR2 (r=0.411, P=0.003) in SLE patients. In SLE patients, serum IL-10 and TNFR2 levels were significantly higher in patients with active disease than in patients with inactive disease (P＜0.05) The AUC using IL-1RA and anti-dsDNA antibody was 0.991 (95%CI:0.979-1.000), with a higher performance (sensitivity 90.7 %, specificity 100.0 %) compared to the use of anti-dsDNA antibody only. The combined model of TNFR2, IL-10 and CRP has the highest AUC ［0.809 (95%CI: 0.678-0.940)］ in distinguishing active and inactive SLE patients, and the sensitivity and specificity were 73.3% and 73.0%, respectively. Conclusion Combination of IL-1RA and anti-dsDNA antibody can be used as biomarkers for diagnosis of SLE. IL-10 and TNFR2 can be used as biomarkers to distinguish active SLE from inactive SLE