Some observations have demonstrated that the possibilities to identify microbial activity in deep subsurface environments are not always following the known limitations for life regarding 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 cumulative negative effect of salinity and temperature. In order to characterize the stresses induced by the combined effect of these parameters, eight selected microbial strains (bacteria and archaea), representative of the main anaerobic metabolisms (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 a synergetic effect on the strains activities. These findings raise the question of the origins of these symmetrical behaviors. Namely, are the microbial mechanisms of resistance and/or adaptation due to the sensitivity of one common structural (membranes) or metabolic target (compatible solutes)?