Objective To investigate the prognostic value of neutrophil-to-platelet ratio (NPR) and mean platelet volume-to-platelet ratio (MPV/PC) in the elderly patients with sepsis. Methods A total of 113 elderly septic patients admitted in our department from January 2018 to May 2019 were recruited in this study. They were divided into survival group (n=78) and death group (n=35) according to their 28-day survival. The clinical data were compared between the two groups. SPSS statistics 25.0 was used for statistical analysis. Cox proportional hazard regression model was applied to analyze the factors affecting the prognosis of patients. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive values of NPR and MPV/PC for 28-day mortality in the cohort. Spearman correlation analysis was employed to make correlation analysis. Results There were no significant differences in white blood cell count (WBC) and procalcitonin (PCT) and C-reactive protein (CRP) levels between the two groups. But NPR and MPV/PC were obviously higher in the death group than in the survival group (P<0.05). Cox proportional regression risk analysis showed that septic shock, high acute physiology and chronic health evaluation Ⅱ (APACHE II) score, high sequential organ failure assessment (SOFA) score, high NPR, high MPV/PC and low platelet (PLT) count were independent risk factors for the prognosis of sepsis in the elderly. ROC curve analysis indicated that the areas under the curve (AUC) of NPR and MPV/PC for predicting 28-day mortality was 0.654 and 0.657, respectively, and the cutoff values were 0.17 (P=0.009) and 0.07 (P=0.008), respectively. Spearman correlation analysis displayed that NPR was positively correlated with APACHE Ⅱ score (r=0.268, P=0.004) and SOFA score (r=0.417, P<0.001), and MPV/PC was positively correlated with SOFA score (r=0.435, P<0.001). Conclusion NPR and MPV/PC have predictive value for the prognosis of the elderly patients with sepsis. These two items are easy to obtain and suitable for early auxiliary initial diagnosis and emergency examination.