COVID-19 represents a serious global threat due to scarcity of definitive cure and its infectious nature. The death rate of COVID-19 patients admitted to hospitals was quite high, and cytokine storms could be the mechanism of severity. Interleukin-6 (IL6) and C-reactive protein (CRP) may predict severity and mortality. We attempted to determine the role of IL6 and CRP as predictors of death in intensive care unit (ICU) patients. This Cross-sectional hospital study included 100 patients admitted to ICUs at Assiut University Hospitals from October 2020 to October 2021. Data including age, sex and comorbidities were recorded, laboratory investigations included CRP, ferritin, and IL6. Data were collected and analyzed. Morality predictors in ICU patients with COVID-19 infection were older age (> 60 years), presence of diabetes mellitus, chest diseases, CRP> 49, IL-6> 70 pg/ml. In conclusion, early ranking and identification of people, who are at risk of death among ICU patients, by monitoring of CRP, IL6, early treatment of cytokine storm, and good management of pre-existing comorbidities would be a very useful approach to reduce the mortality among ICU patients.