Inclusion Criteria:  Provision of signed and dated informed consent form (may be completed by legal proxies for those patients unable to provide consent, i.e. sedation/intubation) Stated willingness to comply with all study procedures and availability for the duration of the study, including follow-up assessments Current ICU admission at Mayo Clinic Rochester with anticipated ICU duration >48 hours after enrollment Current ICU duration < 7 days Patients embedded in the local or regional Mayo Clinic Health System to facilitate post-hospitalization outcome assessment Moderate-to-severe anemia (i.e. hemoglobin concentration < 10 g/dL) at the time of enrollment, with the hemoglobin concentration assessed no more than 24 hours prior to enrollment. If RBC transfusion has been administered between the qualifying hemoglobin assessment and enrollment, a repeat hemoglobin will be required prior to enrollment to ensure that it remains < 10 g/dL.  Exclusion Criteria:  Recent or current iron or erythropoiesis stimulating agent (ESA) use (i.e. darbepoetin, Aranesp, erythropoietin, Epogen, Procrit, Retacrit) within 30 days of enrollment, exclusive of oral iron for general nutritional support (e.g. multivitamin with iron) Severe anemia prior to hospitalization (i.e. hemoglobin <9 g/dL within 90 days of admission) Known allergic reactions to iron or EPO Inability to complete outcome assessments (i.e. not expected to survive hospitalization, unable to make follow-up appointments, non-ambulatory, dementia or other severe cognitive impairment, visual impairment i.e. blind or legally blind) Pregnancy or breastfeeding at time of enrollment Inability to receive pharmacologic venous thromboembolic prophylaxis except in patients with recent surgical or gastrointestinal bleeding Active or suspected thrombosis (i.e. deep venous thrombosis, pulmonary embolism, acute arterial thrombus within 3 months) Uncontrolled sepsis (i.e. <48 hours of appropriate antimicrobial therapy and/or lack of definitive source control) Having received ≥10 units of allogeneic RBCs in the 48 hours before enrollment Acute coronary syndrome or ischemic stroke within 3 months Weight less than 40 kg Concerns with study enrollment expressed by the clinical team Mechanical circulatory support devices