A common and often fatal problem in intensive care units with a range of critical illnesses (CI) is multiple organ failure, which occurs in a predictable sequence (heart, circulation, lungs, kidney), suggesting common drivers. Management is organ support because there are no effective preventative or specific treatments. We contend that mesenteric lymph (ML), draining from the intestine which is subject to injury during CI, is a key driver of organ failure. We have shown that this lymph is able to impair heart function, worsen pancreas inflammation and severely disrupt cellular energy supplies. ML bypasses the liver filter, entering the circulation and adversely impacting vital organs. This project will define the changes in the composition of CI conditioned ML, demonstrating how these are toxic to vital organs and providing a basis for new strategies to prevent and treat organ failure.