Rationale: Survival in sepsis is related to loss of muscle mass and loss of gut mass, contributing to increased translocation of bacteria and sepsis. In clinical relevant models of sepsis, it is unknown in which organs or tissues protein synthesis is reduced in severe sepsis. Therefore we measured protein synthesis of the gut, muscle, liver, and lung in an acute live bacteria (PM) induced hyperdynamic severe sepsis catheterized pig model. Methods: We studied protein synthesis (FSR) of jejunum, jejunal mucosa scraping, ileum, liver, muscle, and lung in 13 pigs with intravenous PM induced hyperdynamic sepsis and 9 healthy controls, using primed-continuous infusion of Phenylalanine (C6) stable isotope. Eighteen hours after start of the sepsis induction, we collected blood samples and tissues. Enrichments of precursor pools and incorporated phenylalanine in protein were analyzed by LC-MS/MS. Data are mean (SE) (in %/hour); stats by unpaired t-test (Prism). Results: We found lower FSR in jejunum and jejunal mucosa in sepsis; Jejunum 0.98%/h (0.08) vs 1.35%/h (0.08) (p = 0.03) and jejunal mucosa 1.53%/h (0.08) vs 1.97%/h (0.1) (p = 0.003). Liver FSR tended to be higher 1.04%/h (0.1) vs 0.85%/h (0.05) (p = 0.091), but FSR in ileum, muscle and lung were not different. Conclusion: Sepsis induced by live bacteria reduces only jejunal, but not ileal, muscle and lung protein synthesis. We hypothesize that nutritional support specifically should aim at improving jejunal protein synthesis.