Mediastinal masses may cause compression of vital structures such as major airways, the superior vena cava and, rarely, the pulmonary artery. The latter could cause cardiorespiratory compromise during or after induction of general anesthesia. We observed a case of a 45-year-old woman with an anterior mediastinal mass that caused severe hypoxemia and hypotension during sternotomy for mass resection, probably by pulmonary artery compression. Immediately upon opening the chest to relieve pulmonary artery compression, oxygen saturation and blood pressure returned to normal. Therefore, we suggest that unexpected hypoxemia and hypotension in a patient with a mediastinal mass can be due to pulmonary artery compression.