Acute pulmonary embolism (PE) is a frequent cause of hypoxemic respiratory failure and presentation to the emergency department. The incidence is on the increase since the COVID-19 outbreak. While COVID infection represents a prothrombotic state, the introduction of COVID vaccines to a lesser extent increased the risk of unprovoked venous thrombus formation and risk of pulmonary embolism. PE is mostly associated with deep vein thrombosis (DVT) and only a few cases of isolated or De novo PE exist in literature. We report two cases of isolated PE associated with COVID-19 vaccinations. We aimed to highlight the need to suspect isolated PE in patients presenting with hypoxemic respiratory failure days to several weeks following COVID-19 vaccination and emphasize the importance of post-discharge follow-up for evaluating chronic thromboembolic pulmonary hypertension (CTEPH).