Background: Erythropoietin in patients under dialysis treatment for renal failure is low which induces anemia. Treatment with recombinant erythropoietin (rEPO) has been used routinely as a supplement treatment for these patients. Immune complexes (IC) react with complement and bind to CR1 on erythrocytes (E-CR1), and are transported to the liver and/or spleen where IC removal and degradation occurs. The erythrocytes then return to circulation where they bind to additional IC. There are some patients whose E-CR1 expression is low with chronic anemia in spite of rEPO treatment. We hypothesized that in hemodialysis (HD) patients altered host defense against infection is associated with low levels of E-CR1. We examined if low E-CR1 in dialysis patients constitutes a risk factor for reduced host defense and poor outcome. Methods: In 95 HD patients, E-CR1 was quantified using a monoclonal E-CR1 antibody and FACS analysis followed by clinical course studies for 5 years. Results: The patients were divided into three groups by E-CR1 level. Percent survival for the low E-CR1 group (53.3%) was significantly lower than the high E-CR1 group (86.4%) (p < 0.01). There were more hepatitis C virus-positive patients within the low E-CR1 group (27.3%) than in the high E-CR1 group (4.7%) (p < 0.05). Furthermore, 10 patients with the lowest E-CR1 levels had severe complications, notably infection at an arteriovenous fistula. Conclusion: A reduced E-CR1 level might be a risk factor for reduced host defense and can be used as a predicting factor for poor prognosis in a HD patient.