Abstract Background Sepsis is defined as a systemic inflammatory response to confirmed or suspected infection. It 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. Objective To correlate between the mean platelet volume in patients with sepsis with C-reactive protein as a prognostic markers. Patients and Methods This is a prospective study conducted on 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 samples were collected during the period from 1st October 2019 to 31st March 2020, MPV results were correlated to CRP, SOFA score and APACHE score. Results The results of the present study revealed: 55.8 % were male and 44.2 % were females. Sex did not affect mortality, no statistical significance found. In this study, MPV was a significant parameter in septic patients. The cut off value for MPV was 10.5 fl which was found to be significant and of a magnitude considered to be clinically useful, with sensitivity 57.1%, specificity 80.8%, p value (0.003) and accuracy 72.5% in predicting mortality. A correlation was found between high MPV, CRP, SOFA and APACHE scores. Therefore, MPV may be used as an auxiliary test in the prognosis of sepsis. Conclusion Initial values of MPV were significantly correlated with CRP, APACHE and SOFA scores and with the estimated rate of mortality.