Pangasiid catfish are important in aquaculture in South East Asia and are cultured in un-aerated ponds. We found these ponds to be severely hypercapnic throughout the growing season reaching PCO2 levels of >30 mmHg. We studied blood acid-base regulation during exposure to realistic levels of hypercapnia in the air-breathing catfish Pangasianodon hypophthalmus to document the rate of HCO3- uptake and to assess its ability to regulate pH during hypercapnia. Using PCO2 values measured in culture ponds in Vietnam,  cannulated fish were exposed normoxic hypercapnia and blood was sampled over time. We show that P. hypophthalmus fully regulates pH within 48 hours of hypercapnia through HCO3- uptake in exchange for Cl-. These results are peculiar because nitrite uptake studies in P. hypophthalmus indicate a low branchial Cl- permeability, and therefore a low regulatory capacity for pH during hypercapnia.