In intensive care units (ICU), vital signs and biomarkers of critically ill patients provide a set of operational parameters for doctors to assess the severity of organ dysfunction and optimize the supporting treatment. Among those organs monitored, the gut is less accessible, and its latent risk is not manageable. There is an emerging need for sensitive and easily measured biomarkers of early intestinal injury. Here, we found plasma fluorochromics can be used to assess the severity of intestinal injury using label-free methods of quantification. In acute mesenteric ischemia-reperusion animal models, ischemia-reperfusion damage can lead to multiple times increase of NADH, flavins, and porphyrin auto-fluorescence in blood. The intensity ratio between NADH and flavin fluorescence can capture early signatures before the occurrence of shock. Using liquid chromatography and mass spectroscopy, we confirmed that riboflavin is primarily responsible for the increased flavin fluorescence. Since endogenous riboflavin in humans is absorbed from the intestine, its increase in plasma validates its association with intestinal injury. In the future, blood fluorochrome detection could serve as a time-course monitoring modality in the emergency department or ICU to assess intestinal damage in various acute illnesses and critical care conditions.