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Microsporidia are spore-forming, obligately intracellular organisms related to fungi. Enterocytozoon bieneusi and 3 Encephalitozoon species (Encephalitozoon cuniculi, Encephalitozoon hellem, and Encephalitozoon intestinalis) are the most common microsporidia identified as pathogens of humans (1, 2). Studies indicate that asymptomatic microsporidial disease occurs in humans, and seroprevalence data suggest that humans may be frequently exposed to these organisms (3–5). Microsporidia cause a spectrum of disease, from self-limiting diarrhea to disseminated, life-threatening infections. Microsporidiosis is recognized predominantly among HIV-infected patients but has more recently been noted in non–HIV-infected individuals as an emerging pathogen (6, 7). Several reports describe microsporidial infections involving organ transplant recipients, but to our knowledge, these infections have not been proved to be transplant-transmitted (8–11). In February 2012, the Centers for Disease Control and Prevention (CDC) was notified of a cluster of 3 transplant recipients with febrile illness onset 7 to 10 weeks after receiving organs from a common donor. Initial evaluation included serologic, molecular, and culture-based assays against a broad range of bacterial, fungal, and viral pathogens. Concomitant illnesses, such as urinary tract infection and organ rejection, were appropriately treated, yet recipients remained ill. Subsequent diagnostic evaluation of recipients suggested infections with a Brucella species that were presumed to be donor-derived. However, despite directed therapy for brucellosis and continued empirical treatment for other infectious etiologies, the patients did not improve, and assistance was requested from public health authorities in determining a common cause for the illness cluster. Kidney biopsy samples sent to CDC from 1 recipient confirmed the diagnosis as microsporidiosis with Encephalitozoon cuniculi, and a public health investigation was initiated to confirm the diagnosis in the other recipients, assess donor and recipient risk factors, and provide therapy recommendations for ill recipients.