Many times a large percentage of CPAP users experience some form of skin irritation while on CPAP therapy. The spectrum of irritation runs from a mild rash along the perimeter of the mask skirt to complete breakdown of the skin, especially on the bridge of the nose, leading to an ulcerated condition. The problem that many CPAP users face is related to a cycle that starts with over-tightening the mask in order to achieve a better fit. When a CPAP user does not achieve a good seal they begin to over-tighten the mask, which then results in more abrasion against the skin along the perimeter of the mask skirt. In addition, the build-up of facial oils, dirt and perspiration contribute to an increase in skin irritation. The typical advice given to many CPAP users in this position is to thoroughly wash the mask and the face prior to mask fitting for the night. The problem with this situation is that many CPAP users that are beginning to experience skin rash or irritation will need to use some kind of facial cream to alleviate the irritation, however, the use of cream will contribute to a loss of seal as the mask skirt needs to be free from foreign substances. This cycle can be a slippery slope which leads to abandonment of therapy if there is not an early intervention to prevent the user from ceasing CPAP therapy.

Another related, and more extreme version of skin irritation while using CPAP therapy is related to a dermatological condition that a certain percentage of CPAP users experience. A certain percentage of CPAP users find that they are allergic to the materials in the mask skirt, leading to some form of "dermatitis" which results from contact with the silicone or other materials in the mask skirt. In this scenario, many CPAP users may find that they experience a range of skin breakouts, rashes, ulcerations and what is sometimes referred to as a "burn." For these users, the hunt for a mask that does not cause this kind of reaction is many times an unsuccessful one as the CPAP user finds that they are allergic to most of the mask skirt material compositions on the market. Some CPAP users may find relief with one particular style of mask, only to find that later the new mask eventually causes irritation as well. The prognosis for these individuals is not good if they do not receive the required intervention, as this path tends to lead toward abandonment of therapy.