As photoprotection with traditional sunscreen presents some limitations, the use of non-traditional treatments to increase skin resistance to ultraviolet (UV) induced damage would prove particularly appealing. The purpose of this pilot study was to test the potential of non-thermal pulsed light-emitting diode (LED) treatments (660 nm) prior to UV exposure in the induction of a state of cellular resistance against UV-induced erythema.Thirteen healthy subjects and two patients with polymorphous light eruption (PLE) were exposed to 5, 6, or 10 LED treatments (660 nm) on an EXPERIMENTAL anterior thigh region. Individual baseline minimal erythema doses (MED) were then determined. UV radiation was thereafter performed on the LED EXPERIMENTAL and CONTROL anterior thigh areas. Finally, 24 hours post-UV irradiation, LED pre-treated MED responses were compared to the non-treated sites.Reduction of erythema was considered significant when erythema was reduced by >50% on the LED-treated side as opposed to CONTROL side. A significant LED treatment reduction in UV-B induced erythema reaction was observed in at least one occasion in 85% of subjects, including patients suffering from PLE. Moreover, there was evidence of a dose-related pattern in results. Finally, a sun protection factor SPF-15-like effect and a reduction in post-inflammatory hyperpigmentation were observed on the LED pre-treated side.Results suggest that LED based therapy prior to UV exposure provided significant protection against UV-B induced erythema. The induction of cellular resistance to UV insults may possibly be explained by the induction of a state a natural resistance to the skin via specific cell signaling pathways and without the drawbacks and limitations of traditional sunscreens. These results represent an encouraging step towards expanding the potential applications of LED therapy and could be useful in the treatment of patients with anomalous reactions to sunlight.