A surge of extended spectrum beta lactamase (ESBL)-producers is being witnessed in the neonatal intensive care units (NICUs). Hence, the present study was conducted to analyze both the bacteriological profile and clinical outcome of neonatal septicemia, and to identify the prevalence and sensitivity of the incriminated pathogens with emphasis on ESBL producers. We conducted this study in the NICU of a tertiary referral hospital over a one-year-period. All neonates with a clinical diagnosis of sepsis (371 participants) were enrolled. Blood cultures were performed, and subsequent cultures of various specimens were done according to clinical suspicion. Antibiotic susceptibility tests were carried out and the neonates were followed up until discharge. Out of the 371 neonates, 137 (37%) had positive blood culture results, of whom 49% died versus only 7.7% of neonates with a negative blood culture (P-value< 0.0001). Low birth weight, prematurity, and the duration of hospital stay were considered as positive blood culture risk factors. Meanwhile, among 85 cultures that yielded Gram-negative pathogens, 16 isolates were identified as ESBL producers with Klebsiella pneumoniae being the most frequently encountered isolate (19.7%). Of the neonates inflicted with ESBL-sepsis, 62.5% died versus 11.6% with non-ESBL sepsis. Judicious antibiotic stewardship together with infection control practices can hinder the spread of drug-resistant pathogens. This is especially compelling among the vulnerable population of the NICUs. Meanwhile, rapid diagnostic modalities and timely antibiotic susceptibility tests are of paramount importance to initiate appropriate therapy which can hugely impact the clinical prognosis.