Air embolization is a potential danger during open heart surgery. To prevent air embolization in incompletely deaired cardiac chambers, flooding of the surgical fields with carbon dioxide (CO₂) is used during cardiopulmonary bypass. CO₂ flooding may be more useful in de-airing for patients undergoing minimally invasive cardiac surgery. We experienced an episode of sudden, severe hypercapnia and respiratory acidosis in a 51-year-old female patient during hypothermic cardiopulmonary bypass for minimally invasive mitral valve replacement. During hypercapnia, hemodynamic and BIS data were stable except for a slight increase in mean arterial pressure. After ruling out other causes of hypercapnia such as oxygenator failure and malignant hyperthermia, severe hypercapnia disappeared gradually after the cessation of CO₂ flooding in the surgical field. No neurologic or cardiopulmonary complications were noted after the operation. We concluded that frequent or continuous CO₂ monitoring may be required during CO₂ insufflation at surgical fields to prevent hypercapnic complications in minimally invasive cardiac surgery.