Abstract : It has been already noticed, by comparing several studies, that the possibilities to identify microbial activity in deep subsurface environments is not always in agreement with the known limitations for life concerning pressure, salinity and temperature. For instance, it is very unlikely to find living microorganisms when temperature and salinity are higher than 70°C and 120 g/L respectively, which demonstrates a combined negative effect of salinity and temperature. In order to understand the different stress effects and the specificity of these parameters, eight selected microbial strains (bacteria and archaea), representative of the subsurface metabolism (methanogenesis, sulfate reduction, thiosulfate reduction, fermentation), have been tested on different temperatures (40, 55 and 70°C), pressures (1, 90 and 180 bar) and salinities (13, 50, 110, 180 and 260 g/L). Experiments were realized accordingly to a set of full factorial plans, and, for each test, the microbial activities were estimated by dosing the main expected metabolic products (CH4, H2S and acetic acid), the pH and the optical density. Results show variable response depending of the strains. Curiously, some species that were not supposed to be piezophile (i.e. surface species) have demonstrated a positive reactivity when the pressure was increased. On the other hand, fermenters and thiosulfate reducers were proven to be the most tolerant metabolisms to the overall range of exposition compared to other strains. Nevertheless, general trends have been also identified: the combined increase of pressure and temperature as well as the combined increase of pressure and salinity did globally provide synergetic effect on the strains activities. This leads to ask whether it is possible that the symmetrical behavior of these stresses is due to the sensitivity of one common structural (membranes) or metabolic target (compatible solutes) that is implicated in the microbial mechanisms of resistance and/or adaptation.