The authors report two cases of prosthetic valve endocarditis due to Coxiella burnetii. The histories were chronic and complex suggesting an auto-immune disease: prolonged recurrent fever despite antibiotic therapy with a biological inflammatory syndrome whilst blood cultures remained negative. The first patient presented with prosthetic valve dehiscence and acute glomerulonephritis. The second patient had coagulation defects with prosthetic valve thrombosis, mesenteric adenopathy and congestive cardiac failure without prosthetic valve dysfunction. In suspected endocarditis with negative blood cultures, serological tests should be extended to intracellular pathogens difficult to identify and justifying specific and prolonged bactericidal therapy (fluoroquinolones, cyclines, rifampincine). Long-term serological surveillance is essential even when the outcome could have led to the termination of antibiotic therapy. Usually, antibiotic therapy provides a bacteriological cure, but treatment has to be continued for at least 3 years, and, in some patients, all their lives. Valve replacement is reserved for haemodynamic complications of the pathology which determine the ultimate prognosis.