Background: The purpose of the present study was to examine the role of mean platelet volume (MPV) in comparison with Sequential Organ Failure Assessment (SOFA), quick SOFA (qSOFA), and Mortality in Severe Sepsis in the Emergency Department (MISSED) scoring systems in predicting hospital mortality among patients with severe sepsis. Methods: This follow-up study was conducted on patients over 18 years with severe sepsis, who were referred to the emergency department. Complete blood count (CBC) samples were sent to the laboratory for MPV measurement. Also, the required samples for determining SOFA and MISSED scores were collected. A senior emergency medicine resident completed the questionnaires upon patient admission and during follow-ups. Hospital mortality was considered as the outcome of the study. All statistical analyses were performed using SPSS version 20. Results: Among 428 patients with severe sepsis, 200 cases were recruited in this study from May 1, 2017, to May 1, 2018. The frequency of hospital mortality was 56 (28%). In the univariate analysis, there was a significant relationship between hospital mortality and age, base excess (BE), MPV, platelet distribution width (PDW), SOFA score, qSOFA score, and MISSED score (P< 0. 0001). Based on the backward conditional method in the multivariate analysis, three variables, including SOFA, qSOFA, and MISSED scores, which showed a significant relationship with hospital mortality, remained in the final model. Conclusion: It seems that MPV plays a less significant role in determining the outcomes of severe sepsis in patients. qSOFA and MISSED scores, especially SOFA score, are of great significance in determining the prognosis of these patients.