Skin damage arising from pollutants in gaseous and particulate matter forms is mainly mediated by oxidative stress. The pollutants directly or indirectly generate free radicals on and in the skin, leading, for example, to MMP up-regulation and damage of collagen fibers. Antioxidants and chelators are used in anti-pollution cosmetics to reduce the harmful effects of free radical generation. We investigated the efficacy of two antioxidants and one chelator in an anti-pollution cigarette smoke model. Free radical generation was measured directly after UV and cigarette smoke exposure ex vivo on pig skin (slaughterhouse waste), by use of Electron Spin Resonance (ESR). Effects of cigarette smoke were compared to those of Urban Dust (NIST-standard). ESR was also used to measure the copper chelation activity of the test products. Following cigarette smoke application in vivo, two markers of lipid peroxidation malondialdehyde (MDA), and squalene monohydroperoxide (SQOOH), were measured from swab solutions taken from the smoke-exposed skin sites. EDTA generated no effect and the non-chelator antioxidant Tocopherol only small antioxidant effects after exposed to cigarette smoke ex vivo as well as in vivo. Only the hydrophilic phenylethanoid H1 showed significant effects. A clear reduction of free radicals ex vivo and further a significant reduction of in vivo lipid peroxide formation was measured. The cigarette smoke model is an ideal method for in vivo assessment of anti-pollution efficacy of topical products with close relation to the real situation of subjects exposed to urban pollution. Further research is required to better understand the role of chelators in anti-pollution cosmetics.