Purpose: The study was done to explore variations in physiologic parameters of the stratum corneum (SC) of the dorsal hand and cord area during early days of life in high-risk newborns. Methods: In this longitudinal study, a total of 77 high-risk newborns were assessed for pH, temperature and hydration of the SC of the dorsal hand and the cord area on the $1^{st}$, $2^{nd}$, $3^{rd}$, $5^{th}$ and $7^{th}$ days of life. Results: Results showed that an acid mantle (AM) was formed in 57.1% for dorsal hand and 35.1% for cord area, implying significant delay regardless of decrease in pH (F=103.60, p<.001), and hydration (F=4.00, p=.003) across days in both areas. Peripheral hypothermia with low hydration level was also observed in both areas. There was a positive relation between hydration and temperature (.14<r<.27, p<.010), and negative relation between hydration and pH in both areas (-.23<r<-.15, p<.010). Antibiotics may play a positive role in AM formation. Conclusion: High-risk newborns may experience delay in acid mantle formation on SC, hypothermia and decreases in hydration on peripheral sites during the first 7 days of life.