Background <p>Isolated pulmonary valve stenosis, of which supravalvular pulmonary stenosis is a subcategory, rarely occurs in live births. Isolated pulmonary valve infective endocarditis is uncommon and typically arises in settings of recurrent transient bacteremia, immunodeficiency, or congenital heart disease. Any infective endocarditis carries high morbidity with complications commonly including congestive heart failure, acute renal failure, and septic emboli among others. Consistent with previously published cases of pulmonary valve infective endocarditis, these cases can be challenging to diagnose and treat.</p> Case presentation <p>We present the case of a 52-year-old male with well-controlled human immunodeficiency virus on antiviral therapy and known non-syndromic congenital supravalvular pulmonary stenosis who developed pulmonary valve infective endocarditis. He originally presented to the emergency room with acute delirium and was diagnosed with <i>Streptococcus agalactiae</i> meningitis and bacteremia due to suspected pharyngitis, but despite antibiotics, progressed to meningoencephalitis and septic shock. His transthoracic echocardiogram was without evidence of infective endocarditis; however, a transesophageal echocardiogram was performed due to a high index of suspicion and confirmed the diagnosis. The patient subsequently required right ventricular outflow tract pericardial patch repair and replacement of the pulmonary valve with a bioprosthetic valve. At follow-up, he was asymptomatic and tolerating rehabilitation.</p> Conclusions <p>Pulmonary valve infective endocarditis can be difficult to diagnose because of limited sensitivity on transthoracic echocardiography and often underappreciated predisposing factors such as simple congenital heart disease. This case provides a reminder to providers of a rare, life-threatening entity that requires a high index of suspicion to diagnose.</p>