Introduction: to compare the clinical, biological, and evolutionary profiles of sepsis with multi-drug resistant and non-multi-drug resistant bacteria in the newborn population. Methods: we performed a prospective, observational, comparative study to monitor all the episodes of blood stream infection, received from the neonatal intensive care, from June to December 2019. Collected data included demographics, symptoms at the time of sepsis, laboratory values, microbiologic results, preliminary and final outcomes. Results: Out of 219 positive blood cultures, 93 episodes were retained. The median age was 6,66 days, 63.4% of newborns were male and 62,4% were premature, 39% of whom had a gestational age of less than 34 weeks. Multidrug-resistant (MDR) bacteria caused 68 sepsis episodes, while non-MDR resistant bacteria caused 25. Bacteremia with MDR organisms, in comparison with non-MDR organisms was associated with poorer preliminary outcomes after empirical antibiotherapy (14% vs 32%; P= 0,001), higher overall mortality rate (20% vs. 51%, P =0.003), and longer antibiotic intake (9.84 vs 7.56 ; P=0,02). The major risk factor found is prematurity (70% vs 40%, P<0,001), No statistical significance was found when other clinical features or laboratory values were compared for infections with MDR vs. non-MDR bacteria. Conclusion: Septicemia with MDR bacteria is more common than non-MDR one in NICU, and it is related to higher morbidity and mortality rates.