We show here that the activities of the proline-specific peptidases DPP4, PRCP, FAP and PREP are dysregulated in septic shock patients and can significantly discriminate between septic shock patients and the selected ICU control group (PREP, FAP and DPP4: AUC values of 0.88 (CI: 0.80–0.96), 0.94 (CI: 0.89–0.99) and 0.86 (CI: 0.77–0.95)). Here, PRCP is linked to Shock.