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Newborn sepsis is a major cause of child mortality across the world. Industrialized countries have made remarkable progress in reducing newborn sepsis and sepsis-related mortality by providing access to hygienic skilled delivery for all women, risk-based intrapartum antibiotic prophylaxis, and high-quality intensive care for newborns that need it. Although resource constraints preclude whole-scale adoption of these strategies in developing countries, there are a number of low-cost proven interventions and promising approaches that have the potential to significantly reduce the burden of neonatal sepsis worldwide.