Introduction: Lactoferrin (LF) is a protective protein present in milk with anti-infective and immune-modulating properties. Objectives: The aim of this study was to determine the association of maternal LF intake and mother's own milk intake in the first 10 days of life on the prevention of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), or death in the first 8 weeks of life in newborns with a birth weight <2,000 g. Methods: A retrospective cohort study was conducted, with the exposure being the consumption of mother's own LF and mother's own milk in the first 10 days of life, and the outcome being LOS, NEC, or death during days 11 and 56 of life, analyzed by Cox regression. Results: Two hundred and ninety-nine infants were enrolled, including 240 with human LF intake information. The average daily human LF intake over days 4-10 of life was 283 mg/kg/day (IQR 114-606 mg/kg/day). The hazard ratio (HR) of mother's own milk LF intake ≥100 mg/kg/day in days 4-10 for LOS, NEC, or death was 0.297 (95% CI 0.156-0.568, p < 0.001); the adjusted HR was 0.752 (95% CI 0.301-1.877, p = 0.541). The adjusted HR of mother's own milk cumulative intake (days 4-10) of 54-344 mL/kg (25-75 quartiles) for LOS, NEC, or death was 0.414 (95% CI 0.196-0.873, p = 0.02). Infants who developed an event (LOS, NEC, or death) had significantly less median daily human LF intake than those that did not (89 vs. 334 mg/kg/day, respectively, p < 0.0001). Conclusion: Consumption of higher amounts of mother's own milk in the first days of life is associated with less infection, NEC, and death. Early human milk intake should be strongly encouraged in all newborns.