Objectives To analyse the immune cell and B-cell receptor (BCR) profiles of patients with SLE, with or without EBV infection, and identify the differences between them.Methods We included two patients with SLE and positive detection of EBV infections (SLE-EBV+), four with SLE with negative detection of EBV infections (SLE-EBV-) and two healthy controls. Single-cell RNA sequencing was used to investigate the heterogeneity of cell populations by combining the transcriptomic profiles and BCR repertoires.Results A total of 83 478 cells were obtained and divided into 31 subtypes. The proportion of CD8+ proliferation T cells was higher in the SLE-EBV+ group than in the SLE-EBV- group. The IFN-alpha/beta pathways were upregulated in most T cells, monocytes and B cells in the SLE-EBV+ group, compared with the SLE-EBV- group. Moreover, T-cell trajectory indicated CD4+ Tregs may play crucial roles in SLE combined with EBV infection. In the BCR heavy chain, the IGHV3 and IGHV4 gene families were frequently present in all groups. Additionally, IgM was the largest component of five Ig isotypes, but its proportion was significantly decreased in the SLE-EBV+ group.Conclusion This study provides a comprehensive characterization of the immune cell profiles and BCR repertoires of patients with SLE, both with and without concurrent EBV infections, contributing to a better understanding of the mechanism underlying the immune response to EBV infection in patients with SLE.