BACKGROUND Total parenteral nutrition (TPN) alters gut cytokines and mucosal immunity and increases intercellular adhesion molecule-1 (ICAM-1) expression, gut neutrophil levels, and mortality after gut ischemia. Supplementation of TPN with glutamine partially supports mucosal immunity by preserving respiratory and intestinal IgA levels, maintaining the proper IgA-stimulating cytokine milieu within the intestine, and reducing intestinal ICAM-1 expression and neutrophil accumulation. This work investigates whether glutamine supplementation of TPN affects mortality in mice after gut ischemic insult. METHODS Thirty-eight mice were randomized to receive chow, TPN, or 2% glutamine-supplemented TPN (GLN-TPN) for 5 days. After feeding their respective diets, gut ischemia/reperfusion (I/R) was induced with superior mesenteric artery occlusion for 30 minutes followed by resuscitation with 1 mL saline. Survival was recorded until 72 hours after reperfusion. RESULTS Survival time was significantly reduced in the TPN-fed mice compared with both chow-fed and GLN-TPN-fed mice (p < .05). Survival at 72 hours after reperfusion was also significantly lower in the TPN-fed mice than in the chow-fed and GLN-TPN-fed mice (p < .05) CONCLUSIONS Glutamine supplementation of TPN significantly improves survival after gut I/R, suggesting modulation of the inflammatory response or improved gut tolerance to low-flow states.