ABSTRACT: When compared to the sublittoral Dungeness crab Cancer magister, the deep-sea Tanner crab Chionoecetes tanneri exhibited lower activities of enzymes involved in some of the processes essential for efficient acid–base regulation. Tissue enzymatic activities were compared between Dungeness crabs held in normoxia and Tanner crabs held in hypoxia—both treatments mimicking typical habitat oxygen levels. In the posterior gill, activities of all forms of ATPase and carbonic anhydrase (CA) were approximately 2- to 13.2-fold lower in Tanner crabs than in Dungeness crabs. CA activity in the heart and white muscle was also significantly lower in hypoxic deep-sea Tanner crabs, while ATPase activity in these 2 tissues was similar between the 2 treatments. Diagnostically, enzymatic activities were compared when both species were held in normoxic seawater, with additional significant differences found in specific white muscle ATPase fractions (amiloride- and N-ethylemaleimide [NEM]-sensitive ATPases) and tissue buffering (β) capacity. When both species were acclimated to normoxia, C. tanneri exhibited mass specific rates of oxygen consumption significantly lower (4.5-fold) than C. magister. Under short-term, strongly hypercapnic conditions (1% CO₂), the Dungeness crab displayed reduced (30 to 40%) branchial ATPase activities, while enzymatic activities in the Tanner crab gill, muscle and heart were refractive to short-term (24 h) hypercapnia, suggesting a minimal ability to tune branchial function to changing environmental conditions. These results support our hypothesis that the deep-sea Tanner crab has a reduced capacity for active transport of acid–base relevant ions, particularly at the gill, and is therefore at a marked disadvantage with respect to iono- and acid–base regulatory capacity. These results add to a growing database documenting the limited ability of deep-sea megafauna to compensate for internal acid–base disruptions associated with introduction of anthropogenic CO₂ into the deep sea.