Abstract Background Blood culture-negative endocarditis (BCNE) is a significant condition associated with cardiac vegetation. It often occurs alongside sepsis, autoimmune diseases, or malignancies, posing a risk of vegetation and embolization. Notable pathogens include Haemophilus species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species. Case Summary A 60-year-old white male Belgian patient presented with worsening dyspnea. His recent medical history included chronic infections over the past 6 months. Transthoracic echocardiography revealed severe aortic stenosis with an 18x12 mm vegetation. Despite normal inflammatory markers and negative blood tests, 18F-fluorodeoxyglucose positron emission tomography with computed tomography excluded malignancy but identified multiple bilateral septic lung emboli. Sputum cultures and tuberculosis PCR (polymerase chain reaction) were negative. Facing the high risk of cardiac embolization and the need for aortic valve replacement, surgery was scheduled with an intraoperative broncho-alveolar lavage (BAL) to investigate the lung lesions. Intraoperative findings confirmed valvular lesions, and a biological aortic valve was successfully implanted. The postoperative course was uneventful. Aortic valve cultures and eubacterial PCR results were negative, but BAL cultures were positive for Haemophilus influenzae), indicating a chronic infection. The patient showed favorable progress at 6 months post-surgery with ongoing antibiotherapy. Discussion This case illustrates a rare BCNE associated with large vegetation and symptomatic Haemophilus influenzae chronic respiratory tract colonization (CRTC). For BCNE cases with negative sputum cultures and suspected bacterial CRTC, we recommend performing BAL cultures for accurate diagnosis.