This descriptive and exploratory observational case series examined intestinal colonisation and subsequent bacteraemia due to ESBL-producing Klebsiella pneumoniae (ESBL-Kp) in preterm neonates in Morocco. Prospective bacteriological cultures and antibiotic susceptibility testing were supported by phenotypic methods, including Brilliance ESBL Agar and the NG-Test CARBA-5 assay, for the rapid detection of ESBL and carbapenemase producers. Molecular analysis using PCR was also undertaken to identify specific resistance genes. A total of 567 rectal swabs were collected from 339 preterm neonates, yielding 293 K. pneumoniae isolates. ESBL-producing strains were identified in 53.6% of the neonates (182/339). Detected resistance genes included blaSHV (26.3%), blaCTX-M-1 (42.8%), blaTEM (30.2%), blaOXA-48 (50.0%), blaNDM(15.3%), and blaVIM (4.9%). Principal risk factors for colonisation were low birth weight (OR 1.69), very preterm birth (OR 6.24), enteral tube feeding (OR 2.02), and prolonged use of third-generation cephalosporins (OR 1.26). Among the neonates studied, 32 (9.4%) developed healthcare-associated bacteraemia, with 56.2% of these cases preceded by intestinal colonisation with ESBL-Kp. Clinically, severe respiratory distress and alveolar haemorrhage were strongly associated with increased mortality (aRR = 29.32 and 4.45, respectively). The findings highlight the clinical importance of early screening to guide infection control and antimicrobial stewardship in neonatal intensive care settings.