A woman in her 30s with a past medical history of hepatitis C and intravenous drug abuse presented to the hospital with a 2-day history of fever and malaise. Initial assessment in the ED revealed hypotension and severe hypoxemia. Initial investigations were notable for a markedly elevated white blood cell count (30.8 × 109/L), mild lactic acidosis (2.6 mM), and a chest radiograph showing a left basal airspace opacity. Initial treatment included empiric antibiotics, intravenous fluid, vasopressor initiation, and high-flow supplemental oxygen. She received a diagnosis of severe sepsis and was admitted to the ICU, where she was subsequently intubated for hypoxemia and decreased level of consciousness. Initial transthoracic echocardiography (TTE), performed by a cardiologist, revealed a large vegetation on the septal leaflet of the tricuspid valve, and a dilated hypokinetic right ventricle (Video 1 Sets 1 and 2). The interatrial septum was not well visualized by TTE, and an atrial septal defect (ASD) could not be to be excluded because of poor apical and subcostal windows. Blood cultures returned positive results for methicillin-sensitive Staphylococcus aureus, confirming infective endocarditis. Chest CT imaging also revealed multiple septic emboli to her lungs, but her burden of parenchymal disease was not believed to be the primary contributor to her hypoxemia. Despite all attempts at optimizing antibiotic therapy, mechanical ventilation, and hemodynamics, the patient continued to deteriorate.