Fever of unknown origin (FUO) in hemodialysis (HD) patients represents a diagnostic challenge because differential diagnosis includes diverse etiologies. Causes of FUO in the general population can be classified into 3 diagnostic categories: infections, tumors, and noninfectious inflammatory diseases. Also, chronic HD patients may have additional problems such as infections, the risk for which may be increased by the immunosuppression associated with uremia, vascular access-related infections, and nosocomial infections. Moreover, patients with chronically failed kidney transplants can have low-grade fever and abdominal pain, and if inflammation of the allograft is severe enough, it may result in a spontaneous rupture. Hence, it is important to rapidly recognize, diagnose, and manage these complications. In the present study, we report a case of FUO in an HD patient with a failed graft and discuss clinical approach and management of these patients.