Background: sepsis is a major cause of morbidity and mortality, and the incidence is rising, probably due to the growing elderly population, antibiotic resistance, immunosuppressive medication and, invasive surgery. Pneumonia is the most common infection leading to sepsis, followed by urinary tract infections and abdominal infections. These infections are usually localized and controlled by the immune system, but they can sometimes spread and cause sepsis. Mean platelet volume (MPV) is a measurement that describes the average size of platelets in blood. MPV is ordered routinely as part of the complete blood count panel by an automated flow cytometry machine. In septic shock, most of the coagulation factors are depleted and platelet count is decreased, a close relationship between sepsis severity and thrombocytopenia has already been documented. Aim of the Work: this work aimed to find a relation between the mean platelet volume and mortality in patients with sepsis in correlation with C-reactive protein and total leukocyte count. Methods: 80 adult critically ill patients of both sexes with sepsis and sever sepsis who admitted to the units of Critical Care Medicine Ain Shams University Hospitals. The mean platelet volume (MPV) evaluated and correlated to both total leukocyte count (TLC) and C-reactive protein (CRP) on a daily basis starting from the day of admission and over 14 days. In addition, patients observed regarding outcomes including mortality and discharge from ICU. Results: MPV was able to detect sepsis prognosis with high statistical significance from admission, CRP also was a good predictor and on the contrary TLC had poor prognostic value on admission and after 24 hours, but for the whole hospital stay a significant association was found. Conclusion: elevated MPV on admission is an important marker for sepsis diagnosis and prognosis. Progressively elevated MPV during hospital stay correlates well with mortality. Decreased platelet count after admission is significantly associated with mortality in septic patients. MPV and platelet count can be used as prognostic markers for sepsis and indicators of mortality on daily basis.