Objective To evaluate the value of serum copeptin combined with acute physiology and chronic health status scoring system III (APACHEIII) in the assessment of the severity and prognosis of patients with severe acute pancreatitis (SAP). Methods Sixty-six patients with SAP admitted to the hospital were enrolled in the studyfrom June to May 2018.The APACHE III score was performed at the admission. The serum copeptin levels were measured. The APACHE III score and serum copeptin levels were analyzed for the relationship between the condition and prognosis of the patients. Results With the increase of APACHE III score, the serum copeptin levels of SAP patients also showed an upward trend, and the difference of the serum copeptin levels among each segment was statistically significant (P<0.05). The APACHEIII score and serum copeptin levelsof the surviving patients were significantly lower than those of the died patients (P<0.05). the="" optimal="" cut-off="" value="" of="" the="" apacheiii="" score="" was="" 60="" points="" the="" optimal="" cut-off="" value="" of="" serum="" copeptin="" levels="" was="" 3.48="" ngml.="" the="" areas="" under="" the="" roc="" curve="" of="" apache="" iii="" score="" and="" the="" serum="" copeptin="" level="" and="" the="" prognosis="" of="" sap="" patients="" were="" 0.926="" and="" 0.878="" respectively="" p="">0.05). The area under the ROC curve of the combination of APACHE III score and the serum copeptin level and the prognosis of SAP patientswas 0.956, and the accuracy was greater than any of the individual predictions (P<0.05). Conclusion The serum copeptin levels and APACHE III scores can be used to determine the severity and prognosis of SAPpatients, and the combined determination of the two can significantly improve the accuracy of the prognosis of SAP patients.