Abstract : Transfusion of packed red blood cells (RBC) is commonly indicated in septic patients to improve tissue oxygen delivery. Besides uncertain benefits, RBC transfusions carry immunomodulatory properties likely to increase the susceptibility to further ICU-acquired infections or the mortality rate. The aim of this study is to address the impact of RBC transfusion on ICU-acquired infections and mortality in septic shock patients.This was a 10-year (2008-2017) monocenter retrospective study. All consecutive adult patients diagnosed for septic shock within the first 48 hours were included. Septic shock was defined as a microbiologically proven or clinically suspected infection, associated with acute circulatory failure requiring vasopressors. The number of packed RBC and the transfusion day were recorded. The diagnosis of nosocomial infections was based on current international guidelines. Patients alive at day 3 were evaluated for the risk of ICU-acquired infections. The determinants of ICU-acquired infections and 30-day mortality were addressed in a multivariate time-dependent Cox regression analysis.Among 1152 patients admitted for septic shock, 63% were males, the median age was 69 (57 79) years old and the crude 30-day mortality rate was 31.5%. Overall, 512 patients (44%) received RBC transfusions, with a median of 3 (2 6) units. In multivariate analysis, transfusion was independently associated with prior immunosuppression (OR=1,57, 95%IC [1,21 - 2,04], p=0,001), with chronic kidney disease (OR=1,89, 95%IC [1,30 - 2,74], p=0,001) and a higher admission SOFA score (OR=1,03, 95%IC [1,01 - 1,06], p=0,007). 1038 patients were alive at day 3, of whom 253 (24%) developed ICU-acquired infections. Among them, 197 (78%) patients had received RBC prior to the episode of ICU-acquired infection. In multivariate analysis, RBC transfusion was independently associated with the development of ICU-acquired infections (OR=1,88, 95%IC [1,21-2,93], p=0,005). 30-day mortality was significantly higher in patients receiving RBC (37,6% vs. 27,8%, p<0,001). In multivariate analysis, RBC transfusion was independently associated with 30-day mortality (OR=1,50, IC95% [1,07-2,09], p=0,02).Transfusion of RBC in septic shock patients is associated with an increased risk of ICU-acquired infections and 30-day mortality. These results support a restrictive RBC transfusion policy in septic shock patients.