Background: Sepsis is one of the main causes of morbidity and mortality in neonates., Objective: To identify the risk factors for neonatal sepsis in a neonatal unit from March to October, 2016., Methods: Case-control study. The factors analyzed were: a) neonatal factors such as: type of delivery, sex, birth weight, gestational age, criteria for systemic inflammatory response syndrome, type of sepsis (early or late) and blood culture result; B) invasive methods such as: central catheterization, total parenteral nutrition, umbilical catheterization and mechanical ventilation; C) maternal factors such as: number of prenatal controls, infection during pregnancy, premature rupture of membranes, maternal age and maternal fever. Odds Ratio was used to determine association., Results: For the development of early-onset sepsis, significant risk factors were: thermodynamic imbalance, tachycardia and maternal fever. With regard to late-onset sepsis, significant associations were found for thermodynamic imbalance, umbilical catheterization, mechanical ventilation and insufficient prenatal care., Conclusions: Thermodynamic imbalance, tachycardia, mechanical ventilation, umbilical catheterization, maternal fever, and insufficient prenatal care were the probable risk factors associated with neonatal sepsis.