Introduction: - Neonatal sepsis remains a serious problem in any neonatal intensive care unit (NICU). Bacterial organisms have developed increased resistance to commonly used antibiotics. The aim of our study was to determine the multidrug resistance sepsis in neonates and their antibiotic sensitivity Subject & methods: This single centre cross sectional study was conducted from the May 2020 to Nov 2020 in pediatric department, Ziauddin University Hospital, Karachi. All patients who fulfilled the inclusion criteria were included in the study. After ethical approval and informed and written consent, multiple sets of blood cultures were sent and antibiotic sensitivities were then assessed on the bacterial isolate to reach the outcome i-e frequency of multidrug resistance. Results: - Total of 185 neonates admitted in neonatal units with sepsis were included. 72 neonates (38.9%) were males & 113 (61.1%) were females with the mean age of 13.810+7.865 days. The Multidrug resistance (MDR) was seen in 90 neonates (48.6%). Conclusion: There is an alarming increase in frequency multidrug resistance to the commonly used antibiotics, it increases with the increase in age of neonate and predominant in female gender. Keywords: Sepsis, Multidrug Resistance, Neonates, Antibiotic Sensitivity