Background. Early administration of colostrum is beneficial because of the number of its immunologic components. The problem with very low birthweight (VLBW) patients is the establishment of early, tolerated, and sustained feeding. The study aimed to determine if early initiation of colostrum through oropharyngeal administration within the first hour of life reduces the risk of late-onset sepsis (LOS) among VLBW newborns.Methods. In this single-blinded randomized control trial, 84 VLBW infants with pediatric aging equal to greater than 28 weeks requiring oxygen support were enrolled. They were allocated to receive either pasteurized colostrum via oropharyngeal administration (treatment group) or none (control group). The occurrence of LOS, duration of ventilator use and oxygen support, time to reach full feeds, length of NICU stay, the occurrence of NEC, and mortality were documented.Results. A significantly greater proportion of patients who developed LOS were noted in the control group (n=38 (90.4%)) than in the treatment group (n=30 (71.4%)) (p=0.013). The use of colostrum, had a protective effect for LOS (RR=0.77; 95% CI=0.63-0.94). There were no significant differences in the secondary outcomes. Still, there was a trend towards a lower proportion of mortality (p=0.08), shorter duration of ventilator use (p=0.24) and oxygen support (p=0.17), shorter time to reach full feeds (p=0.30), and shorter NICU stay (p=0.33) in the treatment group.Conclusion. Patients given pasteurized colostrum had significantly less occurrence of LOS. The treatment group had a lower mortality rate, shorter ventilator use and oxygen support duration, faster time to reach full feeds, and shorter NICU stay, but the differences were not statistically significant. Oropharyngeal administration of pasteurized colostrum within the first hour of life reduces the risk of LOS among VLBW infants admitted to the NICU.