ABSTRACT: Intravenous (IV) resuscitation of burn patients has greatly improved outcomes and become a cornerstone of modern burn care. However, the heavy fluids and vascular access required may not be feasible in austere environments, mass casualty, or delayed transport scenarios. Enteral resuscitation has been proposed for these situations; we sought to examine the effectiveness of this strategy on improving burn-induced kidney injury. Anesthetized Yorkshire swine sustaining 40% TBSA full-thickness contact burns were randomized to three groups (n = 6/group): fluid deprivation, ad libitum water access, or 70 mL/kg/d Oral Rehydration Salt solution (ORS). Urine and blood were collected at baseline (BL), 6, 12, 24, 32, and 48h post-burn, at which point tissue was harvested and CT angiography performed. Although fluid consumption by ad libitum and ORS groups were matched (132±54mL/kg versus 120±24mL/kg, respectively), ORS intake increased urine output compared with water and no water (47.3±9.0 mL/kg versus 16.1±2.5 mL/kg, and 24.5±1.7 mL/kg respectively). Plasma creatinine peaked 6h following burn (1.67±0.07mg/dL) in all animals, but at 48h was comparable to BL in animals receiving water (1.23±0.06mg/dL) and ORS (1.30±0.09mg/dL), but not fluid deprived animals (1.56±0.05mg/dL) (P<0.05). Circulating levels of blood urea nitrogen steadily increased, but also decreased by 48h in animals receiving enteral fluids (P<0.05). Water deprivation reduced renal artery diameter (-1.4±0.17mm), whereas resuscitation with water (-0.44±0.14 mm) or ORS maintained it (-0.63±0.20 mm;P< 0.02). Circulating cytokines IL-1?, IL-6, IFN?, and GM-CSF were moderately elevated in the fluid-deprived group. Taken together, the data suggest that enteral resuscitation with ORS rescues kidney function following burn injury. Incorporating enteral fluids may improve outcomes in resource-poor environments and possibly reduce IV fluid requirements to prevent co-morbidities associated with over-resuscitation. Studies into different volumes/types of enteral fluids are warranted. While ORS has saved many lives in cholera-associated dehydration, it should be investigated further for use in burn patients.