Four independent immune subsets (CD45RA−CX3CR1+CTLA4+CD4+ T cells, CD45RA−17A+CD4+ T cells CD15+CD14+ monocytes, and Ki67+ B cells) were increased in sepsis and provide a predictive model for diagnosis with area under the receiver operating characteristic curve, AUC 0.90 (95% confidence interval, CI 0.82–0.98) in the discovery cohort and AUC 0.94 (95% CI 0.83–1.00) in the validation cohort. Here, CTLA4 is linked to Sepsis.