PURPOSE: The study was conducted to investigate the skin hydration level in various body sites and identify the influencing factors in neonates. METHODS: An exploratory comparison study was designed to measure the stratum corneum hydration, using a National DM-R2 on the forehead, abdomen, buttocks, and the back of the hands and feet of 198 neonates including 92 premature infants. RESULTS: The results showed 32.7%-36.5% of stratum corneum hydration for all sites. Premature infants revealed a higher hydration level on the peripheral sites (dorsal hand and feet) than those of the full-term infants, possibly resulting from therapeutic regimens including an incubator or radiant warmer. Infants in an incubator showed a higher hydration level than those in radiant warmers, suggesting more attention to fluid management for infants in the open environment. In addition, all stratum corneum hydration measurements except one, from the forehead, showed a positive correlation with postnatal age in full-term infants while showing no relation to any measurements in premature infants. CONCLUSION: The study demonstrated the very low skin hydration levels in hospitalized neonates, particularly in premature neonates with more susceptible skin hydration instability despite therapeutic interventions for fluid balance. More vigilant fluid management is imperative in neonates, particularly those in the open environment.