Surgical resection of obstructive tracheal tumors can be challenging to cardiothoracic surgeons and anesthesiologists. It is often difficult in these cases to maintain oxygenation by face mask ventilation during induction of general anesthesia. Also, the extent and location of these tracheal tumors can preclude conventional induction of general anesthesia and subsequent successful endotracheal intubation. Peripheral cardiopulmonary bypass (CPB) under local anesthesia and mild intravenous sedation may be safe to support the patient until securing a definitive airway. We describe a case of a 19-year-old female with a tracheal schwannoma, who developed differential hypoxemia (Harlequin, or North–South, syndrome) after institution of awake peripheral femorofemoral venoarterial (VA) partial CBP.