BACKGROUND Patent Foramen Ovale (PFO) is an important part of fetal circulation. It allows the oxygenated blood from the umbilical cord to bypass the lungs. PFOs usually close after birth due to the sudden change of the hemodynamics associated with the expansion of the lungs however they are known to persist in about 25% of the total population. One of their rare manifestations is Platypnea-Orthodeoxia Syndrome (POS) that presents as dyspnea upon assuming an upright position, which improves upon recumbency, accompanied by hypoxemia. CASE REPORT We report a case of a 63-year-old man, known to have systemic lupus erythematosus (SLE) and positive anti-phospholipid antibodies but with no prior thrombotic events, admitted with symptoms of SARS-COV2 infection, and developed symptoms of Platypnea-Orthodeoxia Syndrome during his hospitalization, further evaluation by a transthoracic echocardiography revealed he had PFO with a right-to-left shunt which was treated successfully with percutaneous device closure. CONCLUSIONS Platypnea-Orthodeoxia Syndrome (POS) can be associated with various cardiac defects resulting in right-to-left shunts and other non-cardiac pathologies such as pulmonary AV malformations, lung parenchymal diseases and hepatopulmonary syndrome. In cases of cardiac right-to-left shunts Contrast-enhanced Transthoracic Echocardiography (TTE) can effectively diagnose Platypnea-Orthodeoxia Syndrome, and percutaneous closure has shown to be an efficacious treatment option in alleviating the symptoms. This case report highlights the necessity of actively exploring the possibility of PFOs with right-to-left shunts in patients exhibiting POS symptoms, while considering other potential aetiologies.