Nowadays the increases of life expectation in developed world has radically changed people demand and their shopping basket. Since medical research has assuring physical wellness until old age, today people ask not only to stay healthy but also to look young. For this reason in the last decades cosmetic research has literally exploded. New generation cosmetics has appeared on the market and small companies started to develop plasma devices for skin care. Although cold plasma is already used in cosmetics, very little is known about the beneficial mechanism that lead to skin renewing. Cold plasma in fact could produce opposite effects on cells. It could either lead to cell death or stimulate their growth. We have also demonstrated that respecting skin microenvironment and particularly its physiological oxygen level (called physioxia) in in vitro experiments is crucial to be as close as possible to in situ skin [1, 2]. It is especially important for cold plasma treatments as the level of oxygen is closely related to the production of reactive oxygen and nitrogen species (RONS), components of the produced plasma. In this work, we characterized the chemico-physical properties of a He plasma gun [3, 4] (run at 14kV, 2 kHz, He flow of 0.5 sml at 10 mm above target) and its effects on culture media and on skin cells. In particular we analyzed O 2 partial pressure (see Fig. 1), RONS species produced, pH modification, effects on dissolved O 2 levels and electric field generation in order to understand plasma treatment consequences and to define the best settings to achieve a stimulating effect on skin cells. This will be first evaluated in physioxia versus normoxia, by assessing cell viability and motility on human keratinocytes and dermal fibroblasts. These results bring new elements to better understand the physiological response of skin cells to plasma treatment and will help to develop new strategies for cosmetical use. Fig. 1: O 2 pressure and temperature variations versus time in medium (7mm high) in a well of 96 well plate This work was supported by ARD 2020 Cosmetoscience PLASMACOSM project.