Clinical characteristics were similar between the two groups, except for a worse SOFA score at day 1 in decedents. Presepsin at day 1 was significantly higher in decedents (2,268 (1,145 to 4,305) pg/ ml, median (Q1 to Q3)) than in survivors (1,184 (855 to 2,158) pg/ml, P = 0.001), while PCT did not differ (18.5 (3.3 to 45.7) vs. 10.8 (2.6 to 46.4) ng/ml, P = 0.31). Presepsin decreased over time in survivors, but remained elevated in decedents (974 (674 to 1,927) vs. 2,551 (1,438 to 5,624) pg/ml at day 7, P = 0.02 for time-survival interaction); PCT decreased similarly in the two groups (P = 0.19). Patients with early elevated presepsin had worse SOFA score, higher number of MOFs, hemodynamic instability (lower mean arterial pressure at baseline and after 6 hours), and mortality rate at 90 days (75% vs. 42%, log-rank P < 0.001). The association between presepsin and outcome was more marked in patients with late enrollment (6 to 24 hours), and in septic shock. Early presepsin had better prognostic accuracy than PCT (AUROC 0.69 vs. 0.56, P = 0.07), and improved discrimination over SOFA score, especially in septic shock.