Background: High mortality and morbidity rates are associated with neonatal sepsis in preterm and low birth weight infants. Aside from controlling the nosocomial infection, intervention for reducing the risk of sepsis is demanded. The best nutrition for preterm infants is breast milk. Bioactive compounds found in it, such as antibacterial, antiviral, and anti-inflammatory activities not only for immunity against the infection but also for growth, and development. Objective: To investigate the effect of breast milk against the risk of neonatal sepsis in preterm and low birth weight infants. Methods: We conducted an electronic search through several databases including PubMed, Web of Science, Science Direct, and Scopus. We performed an analysis on nutritional feeding and volume of breast milk and late-onset sepsis from ten potential observational studies. Results: Breast milk significantly reduced the risk of sepsis in preterm and low birth weight infants (pooled RR 0.70; 95 % CI 0.55 -0.88, p = 0.002). In addition, when we performed subgroup analysis, we found that breast milk volume > 50ml/kgbw/day also reduce the risk of sepsis with pooled RR 0.61(95% CI 0.46-0.8, p=0.0004). Conclusion: Low birth weight and preterm infants had a lower risk of neonatal sepsis when they got breastmilk. To preserve the supply of breastmilk, health professionals should support and encourage mothers who were breastfeeding.