Infective endocarditis (IE) has high mortality, partly due to delayed diagnosis and treatment. Currently, no biomarker can identify IE in patients with fever and clinical picture of infection. To find putative biomarkers we analyzed serum levels of two proteins found in cardiac valves, osteoprotegerin and fibulin-1 among 689 and 696 patients on clinical suspicion of IE, respectively. In addition, proteomic analyses were performed in 24 patients with bacteremia, 12 patients with definite IE and 12 patients with excluded IE.