Abstract Background Extracorporeal membrane oxygenation (ECMO) is increasingly being used for critically ill patients with cardiopulmonary failure. Air in the ECMO circuit is an emergency, a rare but fatal complication. Case presentation: We introduce a case of a 76-year-old female who suffered from cardiac arrest complicated with severe trauma and was administered veno-arterial extracorporeal membrane oxygenation. In managing the patient with ECMO, air entered the ECMO circuit, which had not come out nor was folded or broken. Although the ECMO flow was quickly re-established, the patient died 6 hours after initiating ECMO therapy. Conclusions In this case report, the reason for the complication is drainage insufficiency. This phenomenon is similar to decompression sickness. Understanding this complication is very helpful for educating the ECMO team for preventing this rare but devastating complication of fatal decompression sickness in patients on ECMO.