Background: Systemic lupus erythematosus (SLE) was characterized by extreme clinical heterogeneity and flare unpredictability. The immune homeostasis was the basis to maintain SLE stabilization. However, there were limited data to clarify the association between the SLE flare and immunophenotypes. Methods: Peripheral blood mononuclear cells were obtained from 93 SLE patients with low disease activity state (LDAS) and 66 healthy individuals. Circulating B and T subsets were defined using flow cytometric analysis as recommended by the Human Immunology Project Consortium. Based on the date of these subgroups cells, immunophenotypes of 93 LDAS patients were distinguished by principal components analysis (PCA) and cluster analysis. Results: Compared with healthy controls, the LDAS patients had higher proportions of plasma cells, double negative B cells, naïve B cells, CD8+T cells and regulatory T cells, and lower proportions of unswitched memory B cells and CD4+T cells. PCA indicated that the immunophenotypes had the abnormalities of the T and B cell axes among these LDAS patients. Cluster analysis showed that these patients could be divided into 3 groups: memory B cells group, naïve B cells group and T cells group. The patients in memory B cells group had the lower flare risk, SLEDAI scores, IgG levels and prednisone dose compared with the non-memory B cells group (including naïve B cells group and T cells group) patients. Conclusion: The peripheral immunophenotypes were associated with the SLE flare in the LDAS patients. The memory B cells dominant group patients had low risk of flare.