A few cases of platypnea-orthodeoxia syndrome have been described in the literature, some of them after thoracic or upper abdominal surgeries. In most cases, hypoxemia in the upright or sitting position, which is the main clinical symptom for this uncommon diagnosis, is usually related to a dynamic right to left cardiac shunt induced by anatomical changes in the relative position between the inferior vena cava and the atria in the presence of a patent foramen ovale. In this case report, we describe a situation in which platypnea-orthodeoxia syndrome developed acutely before surgery but that became severely exacerbated after an open urologic surgery without a clear acute anatomical change that could be responsible for triggering the syndrome. This case might suggest that the pathophysiology of acute platypnea-orthodeoxia syndrome is not completely elucidated and that other possible triggers for acute clinical manifestation in addition to acute anatomical thoracic changes must be explored.