Our results suggest that Nrp‐1 is beneficial for TGF‐β1 to enhance the stability of CD4+CD25+ Tregs, and may represent a novel therapeutic target with the potential to improve the CD4+CD25+ Tregs‐related primary negative immunoregulation associated with the TGF‐β1/Smads signaling pathway in sepsis. Here, TGFB1 is linked to Sepsis.