The striped catfish (Pangasianodon hypophthalmus) is a facultative air-breathing fish that is cultured in freshwater culture systems in Mekong Delta, Viet Nam. We report the effects of increased CO2 concentrations (7, 14, and 21 mmHg) and CO2 at different temperatures (27, 30, and 33 ◦C) on: (i) acid-base status and stress indicators (plasma glucose and cortisol); and (ii) growth parameters including weight, daily weight gain (DWG), specific growth rate (SGR), food conversion ratio (FCR), and digestive enzyme activity in P. hypophthalmus juveniles. The results show that there were stress responses via increases of glucose and cortisol concentrations, sharp decreases in pHe (extracellular pH) and increases in PaCO2 (partial pressure of CO2). Acid-base regulation appeared at the latter stage of CO2 exposure (from 24 h) at elevated temperatures with a related increase of plasma HCO3􀀀. Digestive enzyme activities tended to reduce, typically pepsin at the high CO2 exposures of 14 and 21 mmHg  after 60 days. Although survival rate fluctuated from 95 to 100% for all treatments, the lowest weight (56 g/fish) was found in the treatment of 21 mmHg CO2 whereas the control was 75 g/fish after 3 months of culture. In addition, DWG and SGR were relatively similar between the treatments of 7 mmHg CO2 and 14 mmHg CO2 at all three temperatures, whereas higher CO2 concentration led to significantly higher FCR at all CO2 exposures. In conclusion, there were no significant negative impacts of elevated temperatures (27–33 ◦C) and CO2 exposures (7–21 mmHg) in isolation and in combination on physiological responses, although there was decreased growth performance at the highest concentration of CO2 (21 mmHg).