Background: Coagulase-negative Staphylococci (CoNS) are opportunistic pathogens causing severe hospital-acquired infections. This study aimed to determine the frequency of linezolid-resistant CoNS (LRCoNS) in intensive care unit (ICU) infected patients and the related resistance genes. Methods: Seventy CoNS were isolated from 254 different clinical samples from ICU patients. They were identified by conventional methods; species were identified by API. Antimicrobial susceptibility test (AST) by disc diffusion method was performed for CoNS isolates. Methicillin resistance was identified by resistance to cefoxitin (30 μg) disc. Linezolid resistance was confirmed by measuring the minimal inhibitory concentration (MIC) using E-test strips (0.016-256 μg/ml). Three resistance genes (cfr, optrA and poxtA) were tested for the LRCoNS by PCR. Results: Among the 70 CoNS isolates, three LRCoNS were detected by disc diffusion method and confirmed by MIC (>256 μg/ml). Approximately 71.4% of the isolated CoNS were multi-drug resistant (MDR) and 68.6% were methicillin-resistant (MR). The three LRCoNS isolates (2 Staphylococcus (S.) epidermidis and one S. haemolyticus) were positive for cfr gene and negative for optrA and poxtA genes. Conclusion: The presence of cfr gene in the three LRCoNS isolates could explain the MDR of the three strains. This is considered an alarm for the antimicrobial resistance to the last resort antibiotics in hospital settings. So far, the situation is not threatening. Yet, continuous monitoring is essentially required