Adequate nutritional support is a major challenge in brain injury patients, because malnutrition cannot be reversed by standard enteral nutrition. We hypothesized that an oligomeric formula could improve nutritional status by restoring intestinal trophicity. Eighteen male Sprague-Dawley rats (300-330 g) underwent gastrostomy on day-7 (D-7) and traumatic brain injury (TBI) by hydraulic percussion (D0) and were then fed for 4 days with either a polymeric formula (Sondalis® HP, TBIP, n = 9), or an oligomeric formula (Peptamen® HN, TBIO, n = 9). In addition, a control group of healthy gastrostomized rats was fed the polymeric diet (control, n = 8). All rats were weighed daily. On D+4, the rats were euthanized. Blood was collected for plasma amino acid determination. Organs were removed and weighed. Intestinal morphometry was studied. Protein content was assessed on intestine and muscles. Enterobacterial translocation and dissemination were evaluated. Results were expressed as means ± SEM and compared using analysis of variance+Newman-Keuls test. TBI induced a significant decrease in whole body weight (TBIP vs. control, p < 0.05) that was totally blunted by the oligomeric diet (TBIP vs. TBIO, p < 0.01). Thymus weight significantly decreased after TBI (TBIP vs. control, p < 0.05) and was restored by the oligomeric formula (TBIO vs. TBIP, p < 0.05). Glutamine (GLN) concentration was improved by the oligomeric diet in both plasma (TBIO: 688 ± 19 vs. control: 591 ± 45 and TBIP: 615 ± 42 μmol/L, p < 0.05) and soleus muscle. These results show that the use of an oligomeric diet may limit response to injury after brain injury and could be a simple nutritional strategy in this setting.