Posttraumatic anemia in multiply injured patients is caused by hemorrhage, reduced red blood cell survival, and impaired erythropoiesis. Trauma-induced hyperinflammation causes impaired bone-marrow function by means of blunted erythropoietin (EPO) response, reduced iron availability, suppression and egress of erythroid progenitor cells. To treat posttraumatic anemia in severely injured patients, symptomatic therapy by blood transfusion is not sufficient. Furthermore, EPO, iron, and the use of red cell substitutes should be considered. The posttraumatic systemic inflammatory response syndrome (SIRS) induces posttraumatic anemia. Thus, a worsening of SIRS by a "second-hit" through blood transfusion ought to be avoided.