Background: Postoperative sepsis, which has high morbidity and mortality, is a major problem affecting the outcome of neonatal surgeries. Adequate treatment and preventive measures for sepsis can decrease the morbidity and mortality in neonatal surgeries. Objective: (1) To study the incidence of sepsis in neonatal surgical patients and (2) To study the causative organisms and their sensitivity to antibiotics in such sepsis. Materials and Methods: A prospective, observational study was carried out in the tertiary-care level neonatal intensive care unit of SSG Hospital, Vadodara, Gujarat. Eighty newborns having a major surgery within the first 30 days of life were included in the study. Baseline data of the study participants were collected including antenatal and perinatal histories and evidence of postoperative sepsis. Complete examination and investigations including quantitative C-reactive protein (QCRP), WBC counts, blood culture, and treatment were also included. Conclusion: Incidence of postoperative sepsis in neonates was found to be 73.75%. We found coagulase-negative Staphylococcus aureus to be the most common organism (38%) cultured from blood, followed by Klebsiella (19%) and Acinetobactor (18.2%), which was sensitive to cefotaxime, amikacin, and piperacillin/tazobactam.