Microorganisms may produce substances that disrupt the interaction between platelets and vascular endothelium, which has been associated with atypical hemolytic uremic syndrome (HUS). We present the first reported case of Fusobacterium necrophorum bacteremia that presented initially with atypical HUS. Antimicrobial therapy eradicated the patient's bacteremia, and plasmapheresis restored platelet-endothelial homeostasis. Understanding the pathophysiologic mechanisms involved in atypical HUS would guide the development of more precise therapies.