Platypnea-orthodeoxia is an uncommon syndrome that may occur due to the postpneumonectomy state, cirrhosis of the liver, recurrent pulmonary embolism, and intracardiac shunting. We describe a patient who was found to have a positional change in desaturation after being admitted for dehydration. Workup revealed an atrial septal defect with aneurysm. Following surgical repair, the orthodeoxia resolved. Different mechanisms explain positional desaturation, such as atriovenous malformations at the lung base of cirrhotic patients. In an atrial septal defect, the increased shunting of blood across a malformed septum in an upright position may cause orthodeoxia. This case highlights the necessity of heightened awareness of this syndrome and the need for documenting orthostatic changes in cases of severe hypoxemia.