Objective To explore the peripheral blood CD3+CD56+NKT levels and related mechanisms in patients with systemic lupus erythematosus(SLE). Methods A total of 112 SLE patients(SLE group) admitted to Jiulongpo hospital of traditional chinese medicine from August 2019 to December 2020 were selected, and they were divided into non-active stage(72 cases) and active stage(40 cases) according to SLEDAI score, and 50 healthy volunteers(healthy group) during the same period. Blood samples were taken from the participants and CD3+CD Co-56 Coefficient +NKT levels were determined using flow cytometry. Serum related cytokines were determined using ELISA to analyze the correlation between each index and the disease. Results The peripheral blood CD3+CD56+NKT cell count and proportion in the SLE group were significantly lower than those in the healthy group, and the difference was statistically significant(P＜0.05); the peripheral blood CD3+CD56+NKT cell count and proportion in the SLE group Compared with the healthy group, the difference was statistically significant(P＜0.05). The results of Pearson correlation analysis showed that CD3+CD56+NKT cells were negatively correlated with SLEDAI score, 24hUPQ and IL-4 in SLE patients(r=-0.573, -0.682, -0.374, P＜0.05), but not significantly related to IFN-γ Correlation(r=0.016, P＞0.05). Conclusion CD3+CD56+NKT cells are involved in the immune regulation process of SLE, and their expression level is significantly negatively correlated with the patient's SLEDAI score. CD3+CD56+NKTcells may exert SLE immunoregulation by secreting Th1/Th2 cell-related factors, which is worthy of clinical reference.