Objective To investigate the expression and clinical significance of extracellular nicotinamide phosphate ribose transferase(eNAMPT)and soluble programmed death ligand 1(sPD-L1)in serum of pa-tients with sepsis secondary to severe pancreatitis(SAP).Methods A total of 92 SAP patients admitted to the hospital from February 2019 to February 2022 were selected as(SAP grou),and divided into a sepsis group(42 cases)and a non-sepsis group(50 cases).Moreover,50 patients with mild to moderate pancreatitis who were diagnosed and treated at the same time were selected as the disease control group,and 50 healthy in-dividuals who underwent the physical examination in the hospital during the same pariod were selected as the healthy control group.Enzyme linked immunosorbent assay was used to detect serum levels of eNAMPT and sPD-L1.Pearson correlation analysis was used for correlation analysis.Multivariate Logistic regression analy-sis was used to analyze factors affecting the occurrence of secondary sepsis in SAP.The predictive value of ser-um eNAMPT,sPD-L1 and their combination in the secondary sepsis of SAP was conducted by receiver operat-ing characteristic(ROC)curve.Results The serum levels of eNAMPT and sPD-L1 in the SAP group were higher than those in the disease control group and the healthy control group,and the differences were statisti-cally significant(P＜0.05).The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score,Sequential Organ Failure Assessment(SOFA)score,white blood cell count,C-reactive protein,pancreatic nec-rosis,systemic inflammatory response syndrome,multiple organ failure,serum eNAMPT and sPD-L1 in the sepsis group were higher than those in the non-sepsis group,and the differences were statistically significant(P＜0.05).There was a positive correlation between serum eNAMPT,sPD-L1 and APACHE Ⅱ score,SOFA score in sepsis SAP patients(P＜0.05).Serum eNAMPT and sPD-L1 were independent risk factors for sec-ondary sepsis in SAP patients.The area under the curve(AUC)of the combination of serum eNAMPT and sPD-L1 for predicting secondary sepsis in SAP patients was 0.916(95％CI:0.868-0.947),which was signif-icantly larger than 0.846(95％CI:0.791-0.879)and 0.830(95％CI:0.774-0.861)of the single indicator detections,and the differences were statistically significant(Z=4.129,4.885,P＜0.001).Conclusion The serum eNAMPT and sPD-L1 levels in patients with sepsis secondary to SAP are elevated,which are related to the severity of the disease.The combination of serum eNAMPT and sPD-L1 has high predictive value for sec-ondary sepsis in SAP.