Background OPCs are natural phytonutrients of the flavanol family. The dietary supplement ingredient MASQUELIER's ® OPCs has been demonstrated to exhibit antioxidant, anti-inflammatory and vasculo-protective properties in humans, which suggested potential benefits as a topical formulation for skin health. Exposure of skin to UV triggers oxidative stress in skin tissue that can lead to erythema, skin aging or even cancer. Our previous studies have shown that a specific topical formulation (cream containing MASQUELIER's ® OPCs) can significantly reduce UV-induced erythema in skin of human subjects and in animals, indicating it has antioxidant activity in skin. Objective This study was undertaken to further establish antioxidant activity of the specific OPCs cream formulation in human skin by measuring ultra-weak photon emission (UPE) of skin. UPE measurement in skin is a non-invasive, fairly-sensitive and convenient technique for continuously monitoring oxidative stress (Sauermann, 1999). Methods The study was an open-label study in 25 healthy volunteers. Measurement of skin UPE was performed on the dorsal surface of the subjects’ hands before (spontaneous UPE) and after exposure to UV (UV-induced UPE). The effects of the OPCs cream on spontaneous and UV-induced UPE were measured using a fractionated UV exposure protocol. Results Within each subject, spontaneous UPE of the right and left hand were found to be significantly correlated ( r =0.9; p =0.000). UV-induced UPE of the right and left hand were also significantly correlated ( r =0.87; p =0.000). UV exposure resulted in a long-term (>80 min) increase of spontaneous UPE. This is likely due to depletion of antioxidant capacity of skin, which is quantifiable by the fractionated UV-exposure protocol. Application of the OPCs cream immediately after UV exposure resulted in a significant (approx. 30%) decrease in UV-induced UPE. Topical OPCs application also reduced UV-induced long-term increase in spontaneous UPE, indicating prevention depletion of antioxidant capacity of skin by UV. Conclusions This study indicates that the specific OPCs cream formulation significantly decreases UV-induced oxidative stress in human skin based on UPE measurement, thereby suggesting that regular use of this OPCs cream might protect skin from harmful effects of UV.