The skin properties, structure, and performance can be influenced by many internal and external factors, such as age, gender, lifestyle, skin diseases, and a hydration level that can vary in relation to the environment. The aim of this work was to demonstrate the multifaceted influence of water on human skin through a combination of in vivo confocal Raman spectroscopy and images of volar-forearm skin captured with the laser scanning confocal microscopy. By means of this pilot study, the authors have both qualitatively and quantitatively studied the influence of changing the depth-dependent hydration level of the stratum corneum (SC) on the real contact area, surface roughness, and the dimensions of the primary lines and presented a new method for characterizing the contact area for different states of the skin. The hydration level of the skin and the thickness of the SC increased significantly due to uptake of moisture derived from liquid water or, to a much lesser extent, from humidity present in the environment. Hydrated skin was smoother and exhibited higher real contact area values. The highest rates of water uptake were observed for the upper few micrometers of skin and for short exposure times.