Background: Skin care of sick newborns is important because skin acts as a barrier to prevent neonates from infections which may lead to neonatal morbidity and mortality. The highly technological environment of the neonatal intensive care unit (NICU) makes them vulnerable to loss of skin integrity. In acute care setting maintenance of skin integrity is considered as an established quality indicator representing nursing care. Aim of Study: The study aimed to determine the effect of skin care guidelines on nurses’ knowledge related to skincare and the incidence of skin injuries among neonates. Methodology: Pre-post quasi-experimental study was conducted in the NICU of a private tertiary care hospital. A consecutive sampling technique was used. The intervention comprised educational sessions and demonstrations of skin care practices from AWHONN skin care guidelines. The data on the nurses’ knowledge were collected through self-developed and self-administered questionnaires. Skin injuries were recorded on a checklist through observation for 1 month before and after the intervention. A paired sample t-test was used for comparing knowledge and continuous demographical variables. While the incidence density ratio was calculated for skin injuries. Results: There was a statistically significant improvement in the nurses’ knowledge of skin care from pre (mean 15.06 ± 5.16) to post (mean19.40 ± 5.17) measurement P-value .001. Incidence density rate of skin injuries reduced from 19% to 3% after the implementation of skin care guidelines. Conclusion: Through the implementation guidelines nurses’ knowledge and practices regarding skin care improved while skin injuries among neonates were reduced.