Background: Case Summary: We describe a 35-year-old pregnant woman with known mitral valve prolapse who presented at 21 weeks of gestation with an acute ischemic stroke. Initial etiological work-up, including transesophageal echocardiography, was unremarkable. Ten days later, she re-presented with left-arm pain and neurologic symptoms. Repeat echocardiography revealed multiple mitral vegetations compatible with infective endocarditis. Despite multiple sets of prolonged-incubation blood cultures and extensive serological testing, all microbiological investigations remained negative. Empirical intravenous ceftriaxone was initiated based on the working diagnosis of HACEK endocarditis. A plasma metagenomic cell-free DNA test ultimately identified Conclusion: This case illustrates the diagnostic challenges of culture-negative infective endocarditis in pregnancy and underscores the value of plasma microbial cell-free DNA sequencing as a complementary tool when conventional methods fail. It also emphasizes the need to repeat echocardiography when clinical suspicion remains high and raises the question of antibiotic prophylaxis for high-risk dental procedures in pregnant women with underlying valvular heart disease.