BACKGROUND: Systemic Lupus Erythematosus (SLE) is a typical autoimmune disease characterized by a complex pathogenesis and a strong genetic predisposition. The study of inflammatory response in SLE monocytes is not very clear, and exploring the inflammatory factors of monocytes is beneficial to discover new diagnostic targets. RESULTS: Using scRNA-seq technology, we obtained the quantitative changes in circulating immune cells and various cellular immune metabolic profiles between SLE patients and healthy volunteers. A significant increase in monocytes was observed in peripheral blood of SLE patients. Flow cytometry was employed to validate the types and quantities of circulating immune cells in SLE, corroborating the scRNA-seq results. Monocyte highly expressed IRF1 (interferon regulatory factor 1) in SLE. Previous research proves that IRF1 is widely involved in immune regulation and inflammatory response, and can promote the transcription of a variety of pro-inflammatory cytokines. Additionally, Inflammatory factors secreted by monocytes in serum were measured. The results demonstrated a significant upregulation of IFN-γ, TNF-α, IL-2, IL-6, IL-8, IL-10, IL-1β in the sera of SLE patients compared to healthy controls. CONCLUSION: Our results demonstrate upregulation of monocyte inflammation in circulating immune cells in SLE patients and expands the current understanding of circulating immune cells in SLE. Our study provides a blueprint for future exploration of SLE monocytes, revealing the pathogenesis and inventing new immunotherapies.