Reducing neonatal mortality is a global challenge. This study’s objective was to determine the predictors of mortality in patients with neonatal sepsis. The study was a retrospective cohort study in a Peruvian hospital from January 2014 to April 2022. Neonates diagnosed with sepsis were included. To find predictors of mortality, we used Cox proportional regression models. We evaluated 288 neonates with sepsis; the median birth weight and hospitalization time were 3270 g and seven days, respectively. During follow-up, 18.4% did not survive, and the most common complications were jaundice (35.42%), respiratory distress syndrome (29.51%), and septic shock (12.5%). The most isolated bacteria were Klebsiella pneumoniae. The risk factors associated with higher mortality were prematurity (aHR = 13.92; 95% CI: 1.71–113.51), platelets <150,000 (aHR = 3.64; 1.22–10.88), creatinine greater than 1.10 (aHR = 3.03; 1.09–8.45), septic shock (aHR = 4.41; 2.23–8.74), and admission to IMV (aHR = 5.61; 1.86–16.88), On the other hand, breastfeeding was associated with a lower risk of death (aHR = 0.25; 0.13–0.48). In conclusion, we report a high incidence of death and identify clinical (prematurity, septic shock, admission to IMV) and laboratory characteristics (elevated creatinine and thrombocytopenia) associated with higher mortality in patients with neonatal sepsis. Breastfeeding was a factor associated with survival in these patients.