Background: Recently, sepsis associated with gram negative bacteria (GNB) have increased globally in critically ill patients in which infection by these GNB increases mortality, morbidity, and cost expenditure. A difficult to treat GNBs infections are belonged to multi-drug resistant MDR-Enterobacteriaceae.spp including CRE, since they are susceptible to a limited number of antibiotics. the importance to conserve colistin susceptibility by combination with other available antibiotics (ABs) is an imperative and of an urgent priority of our responsibility to mitigate the emerging of pan-resistant GNB (PR-GNB). The aim of this study is to compare efficacy outcomes of using colistin/high dose meropenem [Group I] with Colistin monotherapy [Group II] in critically ill patients who had sepsis caused by CRE regarding hemodynamics, infectious values, and overall major clinical outcomes in septic critically ill patients. Methods: We perform a retrospective analysis of 102 septic critically ill patients admitted to the adult ICU between April 2017 and April 2019. All patient’s continuous variables were expressed as Mean ±SD by using the independent T-Test. Using of Chi Square test to express categorical variables, as numbers with percentages. Results: the mean overall age of 58.4±9.95 years. 56 subjects (54.90%) were male and 52 subjects (50.98%) were female. Objectively, the hemodynamic parameters were positively and significantly higher in Group I versus Group II. The %∆ CRP: ALB and (NEavg) were in Group II significantly higher than Group I (269%±33%, and 7.12±0.19, 179%±30% and 6.05±0.07, respectively). The 28-day survival was significantly higher in Group I (48 (80.0%)) versus Group II (40 (64.5%)). In contrast, the ICU stay days, early, late, and 28-day mortality overall 28-day ICU mortality was higher in Group II versus Group I. Conclusion: In conclusion, our study has shown that colistin is more effective with a significant positive impact on clinical outcomes when us