Background: Central venous catheters are mandatory invasive devices for optimum caring of critically ill children, but they potentially carry the risk of serious infections. Our prospective surveillance study fostered monitoring Central Line Associated Blood Stream Infection (CLABSI) for more than one year in order to specifically rate CLABSI and its closely related risk factors and the changing profile of causative microorganisms. According to this, our care policies and procedures will be updated and a new care protocols will be developed according the puzzled-out organisms. Subjects and Methods: This study was carried out in Paediatric and Neonatal Intensive Care Units (PICU) and (NICU), Zagazig University Children’s Hospital, Egypt; in the period from September 2017 to January 2019. Definitions were adopted from the CDC’s National Healthcare Safety Network. All clinical and laboratory data where recorded for all patients since central line catheter insertion. Results: CLABSI rate was 24.73/1000 catheter days during hospital stay. Blood culture was positive in 40.3% of patients; predominantly caused by gram -ve bacteria in 53.7% of them represented as Pseudomonas aeruginosa (70.6%), Acinetobacter (17.6%) and Klebsiella (11.8%). risk of mortality was increased by 1.85 folds in CLABSI positive ICU patient. There was significant relation between type, site of CVC, hand hygiene, wearing PPE, and occurrence of CLABSI among the studied patients. Conclusion: Incidence rate of CLABSI in ICUs is relatively high and mainly caused by gram negative multidrug resistant microorganisms. This is strongly related to leniency of the health care providers in implementing the care bundle. The worldwide creeping new profile of multidrug resistant organisms intensively colonized in our ICUs under the umbrella of heroic empirically used antibiotics