Increased anthropogenic input of carbon dioxide into the atmosphere has caused widespread patterns of ocean acidification (OA) and increased the frequency of extreme warming events. We explored the sublethal effects of OA on the hemolymph chemistry and physiological response to acute thermal stress in the American lobster (Homarus americanus H. Milne Edwards, 1837). We exposed subadult lobsters to current or predicted end-century pH conditions (8.0 and 7.6, respectively) for 60 days. Following exposure, we assessed hemolymph L-lactate and calcium concentrations (as indicators of oxygen carrying capacity), ecdysterone concentrations, total protein content, and total hemocyte counts (THCs) as an indicator of immune response. We also assessed cardiac performance in the context of an acute warming event using impedance pneumography. Calcium, total protein, and ecdysterone concentrations were not significantly altered (P ≥ 0.10) by OA exposure. Control lobsters, however, had significantly higher levels of L-lactate concentrations compared to acidified lobsters, suggesting reduced oxygen carrying capacity under OA. THCs were also 61% higher in control versus acidified lobsters, suggesting immunosuppression under chronic OA. Lobsters exposed to acidified conditions exhibited reduced cardiac performance under acute warming as indicated by significantly lower (P = 0.040) Arrhenius Break Temperatures compared to control lobsters. These results suggest that although some physiological endpoints of American lobster are not impacted by OA, the stress of OA will likely be compounded by acute heat shock and may present additional physiological challenges for this species in the face of future change.