Abstract Such as many other reef organisms, giant clams are today confronted to global change effects and can suffer mass bleaching or mortality events mainly related to abnormally high seawater temperatures. Despite its strong ecological and socio-economical importance, its responses to the two most alarming threats linked to global change (i.e., ocean warming and acidification) still need to be explored. We investigated physiological responses of 4-years-old Tridacna maxima specimens to realistic levels of temperature and partial pressure of carbon dioxide ( p CO 2 ) (+1.5°C and +800 μ atm of CO 2 ) predicted for 2100 in French Polynesian lagoons during the warmer season. During a 65-days crossed-factor experiment, individuals were exposed to two temperatures (29.2°C; 30.7°C) and two p CO 2 (430 µ atm; 1212 µ atm) conditions. Impact of each parameter and their potential synergetic effect were evaluated on respiration, biomineralization and photophysiology. Kinetics of thermal and acidification stress were evaluated by performing measurements at different times of exposure (29, 41, 53, 65 days). At 30.7°C, the holobiont O 2 production, symbiont photosynthetic yield, and density were negatively impacted. High p CO 2 had a significant negative effect on shell growth rate, symbiont photosynthetic yield and density. Shell microstructural modifications were observed from 41 days in all temperature and p CO 2 conditions. No significant synergetic effect was found. Today thermal conditions (29.2°C) appeared to be sufficiently stressful to induce a host acclimatization process. All these observations indicate that temperature and p CO 2 are both forcing variables affecting T. maxima physiology and jeopardize its survival under environmental conditions predicted for the end of this century.