Background and Objectives: Carbapenems are considered the last resort to treat several infections, particularly in intensive care units (ICUs). However, increasing carbapenem resistance is problematic because it leads to high morbidity and mortality rates. This study aimed to determine the rate of carbapenem resistance among Gram-negative bacteria collected from patients in ICUs and to identify their resistance mechanisms using phenotypic and genotypic methods. Materials and Methods: Antimicrobial susceptibility testing was carried out using the disc diffusion method among 180 Gram-negative bacterial isolates. Productions of carbapenemases, metallo-beta-lactamases (MBLs) and the harboring of carbapenemase-encoding genes, were detected in 40 selected carbapenem-resistant Gram-negative bacteria (CR-GNB). Results: Of 40 selected CR-GNB isolates, 28 (70%), and 20 (50%) isolates were phenotypically positive for carbapenemase, and MBL production, respectively. Furthermore, 22 (55%) showed amplification of one or more of the carbapenemase-en- coding genes, including blaNDM-1, blaVIM-2, and blaOXA-48. This study described the first emergence of NDM-1 producing Kleb- siella oxytoca in Egyptian ICUs. Conclusion: High incidence of CR-GNB detected in the ICUs in our study area may be attributed to the overuse of antibiot- ics, including carbapenems, and improper application of infection control measures. These findings confirm the need for the application of a strict antibiotic stewardship program.