To assess the efficacy of a weekly dosing schedule of rHuEPO in critically ill anaemia septic patients to increase the erythropoietic response, to reduce the need for RBC transfusion and whether or not would affect the clinical course, length of ICU stay and the final outcome.A prospective, randomized, controlled single center trial.Critical care department of Cairo University Hospital.A total of 60 anaemic septic patients who were admitted to the ICU and met the eligibility criteria were enrolled into the study (30 into the EPO-group and 30 in the control group).All patients received iron starting on ICU day 2. The treatment group received rHuEPO (40.000 U, S.C.), staring on ICU day 2 and continued once weekly for a minimum of 2 doses or until ICU discharge or up to a total of 4 doses. CBC, reticulocytic count, iron variables and routine labs withdrawn and APACHE II and SOFA scores applied on day of admission and subsequently every 3rd day until ICU discharge or death or up to a total of 28 days. Patients received rHuEPO exhibited significant rise in reticulocytic count (by 816% vs 89 % only in control group, P <0.001) and significant increase in Hb concentration (by 25% vs 15% only in control group, P <0.001) and also received less RBC transfusion (58 units vs 72 units in control group, P <0.059). There was significant decrease in APACHE II score in EPO group (P <0.001) while the control group showed significant increase in SOFA score (P <0.003). The administration of a weekly dose of 40.000 units of rHuEPO to critically ill anaemic septic patients is effective in raising their reticulocytic count, Hb concentration and in reducing allergenic RBC transfusion they require. In addition, patients received EPO exhibited a relatively better in-hospital clinical course and a trend toward increased recovery and decreased mortality.