Many mineral waters are known for centuries for treating dermatological diseases but there is little scientific evaluation of the effects of these waters in skin. A total of 17 healthy Caucasian volunteers, including men and women, were enrolled in this study. Two skin sites were marked on each volunteer forearm and irritated with sodium lauryl sulphate at 2% (w/v) kept under occlusion for 24 h with Finn chambers. Afterwards, purified water or São Pedro do Sul (SPS) thermal water were applied to the irritated skin sites, and kept under occlusion for 48 h also with Finn chambers. Transepidermal water loss (TEWL) was used as a measure of the skin barrier function to evaluate the potential anti-irritant effect of the thermal water on skin. Statistically significant differences in the mean TEWL variations were observed for the skin treated with SPS thermal water and with purified water (P = 0.036). The thermal water reduced the degree to which the skin barrier was disrupted compared with purified water alone in 82.4% of the volunteers. The SPS thermal water is anti-irritant and, therefore, can be helpful to relieve skin irritation and in cosmetic formulations to improve the tolerability of the products.