BACKGROUND Infective endocarditis (IE), a systemic infection characterized by bacterial vegetative growths on heart valves and endothelium, often manifests variably and leads to severe complications, sometimes even death. Accurate and timely diagnosis is paramount, yet the variety of symptoms can lead to delays, especially amidst the complexities of the ongoing COVID-19 pandemic. CASE REPORT A 61-year-old woman with a history of mitral valve regurgitation was admitted after a month of low-grade fever, night sweats, and polyarthritis. Initial blood cultures and CT scans were inconclusive. Upon admission, clinical examination uncovered a heart murmur, leukocytosis, and elevated C-reactive protein levels. Further examination by another physician revealed conjunctival hemorrhage and Janeway lesions. Subsequent blood cultures tested positive for Streptococcus oralis, and transesophageal echocardiography revealed mitral valve prolapse with vegetation, leading to a diagnosis of IE. Following a 6-week course of ampicillin, the patient recovered successfully. CONCLUSIONS This case underlines the necessity of maintaining a high index of suspicion and flexible diagnostic approach, particularly in high-risk patients and complex care environments like the COVID-19 pandemic. A single inconclusive test should not preclude a diagnosis, underscoring the importance of repeated testing and comprehensive assessments in timely disease identification.