Abstract Increased greenhouse gas emissions have caused rapid ocean warming (OW) and reduced ocean pH via acidification (OA). Both OW and OA will likely impact marine crustaceans, but they are often examined in isolation. We conducted an environmental-stressor experiment to understand how exposure to current summer conditions (16 °C, pH 8.0), OW only (20 °C, pH 8.0), OA only (16 °C, pH 7.6), or both acidification and warming, OAW (20 °C, pH 7.6), differentially influence thermal physiology and immune response of female subadults of the American lobster, Homarus americanus H. Milne Edwards, 1837. Following a 42 d exposure, cardiac performance was assessed during an acute thermal stress, and lobsters were subjected to a subsequent 21 d pathogen challenge with the bacterium Aerococcus viridans var. homari, the causative agent of gaffkemia. Lobsters under OAW had significantly lower (P ≤ 0.02) Arrhenius break temperatures (ABT), an indicator of thermal limits of capacity, compared to lobsters exposed to all other treatments, suggesting these stressors act synergistically to reduce physiological performance. Individuals from the OW and OAW treatments also had significantly lower (P ≤ 0.035) total hemocyte counts (THCs), an indicator of immune response, and showed a reduced median time to death (by up to 5 d sooner) post A. viridans injection compared to lobsters exposed to current summer conditions. Moreover, nearly twice as many lobsters exposed to OAW lost at least one claw during the pathogen challenge compared to all other treatment groups, potentially increasing the risk of mortality due to secondary infection. Together, these results suggest that OAW will impact the physiology and immune response of subadult H. americanus, potentially influencing successful recruitment to the fishery.