Objective:To determine incidence, severity, characteristics, and causes of anemia and transfusion requirements in medical intensive care patients.Design and Setting:Open prospective clinical study in a 24-bed medical intensive care unit in a tertiary-care university hospital.Patients:Patients (N = 96) treated in the intensive care unit for >3 days.Interventions:None.Measurements:Parameters of erythropoiesis and red blood cell metabolism, including hemoglobin, reticulocyte counts, serum iron, transferrin, ferritin, haptoglobin, vitamin B12, folic acid, and erythropoietin concentrations were determined serially. Diagnostic blood loss and red blood cell transfusions were recorded, and the total blood loss was estimated from changes in hemoglobin concentrations and the amount of hemoglobin transfused.Main Results:The median hemoglobin concentration was 12.1 g/dL at admission and 11.2 g/dL at the end of the intensive care unit stay. A total of 74 patients (77%) suffered from anemia and received 257 red blood cell units, approximately half of which were given within the first 5 days. Three patients who received 19 red blood cell units were admitted with acute gastrointestinal bleeding, but in the remainder, a median total blood loss of 128 mL/d was not (n = 60) or not solely (n = 11) a result of overt bleeding. Diagnostic blood loss declined from a median of 41 mL on day 1 to <20 mL after 3 wks and contributed 17% (median) to total blood loss. Acute renal failure, fatal outcome, and simplified acute physiology score >38 on admission were associated with a 5.8-, 7.0-, and 2.8-fold increase in total blood loss. Reticulocyte counts and erythropoietin concentrations were inappropriately low for the degree of anemia, and plasma transferrin saturation was mostly <20%.Conclusions:Anemia is frequent and results in a high requirement for red blood cell transfusions in the medical intensive care setting. A major proportion of blood loss is not caused by overt bleeding or diagnostic blood sampling but, rather, may result from various other reasons, e.g., occult gastrointestinal bleeding and renal replacement therapy. The erythropoietic response to anemia is blunted, probably as a consequence of an inappropriate increase in erythropoietin production and diminished iron availability.