Background: Occlusion of the skin is a risk factor for development of irritant contact dermatitis. Occlusion may, however, have a positive effect on skin healing. No consensus on the effect of occlusion has been reached. Objectives: To investigate skin barrier response to occlusion on intact and damaged skin. Methods: In study A, the response to occlusion (nitrile glove material) for either 8 hr daily for 7 days or for 72 consecutive hours, respectively, was determined and compared with that of non-occluded skin. In study B, the response to occlusion of for 72 consecutive hours of skin that had been damaged by either sodium lauryl sulfate (SLS) or tape stripping, respectively, was determined and compared with that of to non-occluded pre-damaged skin. Skin barrier function was assessed by measurements of trans-epidermal water loss (TEWL) and erythema. In study A, stratum corneum lipids were analysed. Results: Occlusion of healthy skin did not significantly influence skin barrier function, ceramide profile or the ceramide/cholesterol ratio. Occlusion of the skin after SLS irritation resulted in higher TEWL than in the control (P = 0.049). Occlusion of the skin after tape stripping resulted in lower TEWL than in control skin (P = 0.007). Conclusions: A week of occlusion did not significantly affect healthy skin, but was found to decrease healing of SLS-damaged skin, and to improve healing of tape-stripped skin.