Background: The red blood distribution width (RDW) and Platelet distribution width (PDW) are useful in predicting morbidity and mortality in sepsis. Objectives: to evaluate the prognostic importance of RDW and PDW, and detect the correlation between RDW, PDW and Sequential Organ Failure Assessment (SOFA) score in predicting mortality, length of stay in ICU and need for mechanical ventilation (MV) in septic patients. Methods: In this observational cohort prospective study, 49 patients admitted to the Critical Care Unit at Beni-Suef University Hospital were defined on the basis of qSOFA greater than 2. Upon admission, all patients underwent a series of sepsis monitoring and assessments. CBC, platelet, PDW, RDW and SOFA score were evaluated. Results: The average number of days that septic patients spent in the ICU was 17.94. There is a statistically significant relationship between SOFA score on admission and after 48 hours with the outcome data of mortality, need for ventilation, PDW and RDW, but not with ICU stay days. RDW revealed a specificity of 31.30% and a sensitivity of 82.40%. PDW, revealed a specificity of 68.8% and a sensitivity of 94.1%. The AUC for SOFA was 0.809; the optimal cutoff value was 4.5, with a specificity of 43.80% and a sensitivity of 88.20%. Conclusion: RDW and PDW were found as significant indicators for need for MV, mortality in sepsis. PDW is the gold standard for predicting mortality in high-risk septic patients; better than RDW.