The moisture content of the human skin, but also the loss of water through the skin, the transepidermal water loss (TEWL), plays a significant role in the skin’s health. Various medical indications require the use of a wound dressing. However, how the skin environment changes under a wound dressing has not yet been sufficiently investigated. Skin moisture and TEWL values were measured in 20 healthy volunteers before and after the application of a total of 23 different wound dressings distributed over the back. Significant changes in the parameters from day 1 to day 2 were tested. Wound dressings change the underlying skin environment. Occlusive dressings significantly increase skin hydration and TEWL. The findings could contribute to quantitative analysis and monitoring of topical-wound therapy in the future.