Background: Outcome prediction for surgical patients with sepsis may be conducive to early aggressive interventions. In several studies, changes in the level of numerous biomarkers like red cell distribution width (RDW), platelet count (PC), mean platelet volume (MPV), and platelet distribution width (PDW) have been demonstrated to be associated with mortality in critically ill patients. We aimed at investigating the prognostic significance of dynamic changes in RDW, PC, MPV, and PDW in surgical patients with sepsis.Methods: We prospectively enrolled 110 surgical patients of sepsis in our study admitted to the surgical ward and ICU. We measured RDW, PC, MPV, and PDW on days 1, day 4, and day 8. Receiver operating characteristics (ROC) were generated for prognostic validation of these parameters and mortality in surgical patients with sepsis.Results: We found that higher RDW and PDW on day 1 among non-survivors as compared to survivors on day 1 were significantly associated with mortality. ROC curves showed that RDW and PDW on day 1 could be used to predict mortality in surgical patients with sepsis and it was dynamic changes in PC on day 4 and day 8 along with a change in MPV on day 8, which was significantly associated with mortality.Conclusion: The major findings of our study were baseline value of RDW and PDW on day 1 and continuous decrease in PC and increase in MPV over one week were significantly associated with mortality. So, it is better to monitor dynamic changes in PC and MPV in combination with baseline RDW and PDW. So, these parameters can be promising markers to assess prognosis in surgical patients with sepsis.