Extensive burn injury (>30% total body surface area [TBSA]) leads to significant inflammation and associated organ damage. The spleen is a major reservoir of lymphocytes which decrease systemically post-burn. Abnormal splenic function may relate to the inflammatory response after burn. While intravenous (IV) fluid resuscitation is the current standard for burn care, enteral resuscitation has also shown promise, and may be leveraged to help splenic recovery. However, the effect of resuscitation on the spleen post-burn is largely unstudied. Thirty anesthetized Yorkshire swine subjected to 40% TBSA contact burns were randomized to one of five groups (n=6/group); no fluids, ad lib water, volume-matched Oral Rehydration Salts (ORS) from the World Health Organization, limited-volume (15mL/kg/d) ORS, or IV lactated Ringer’s solution at 2mL/kg/%TBSA/d (IV). Computerized tomography (CT) scans were performed before and 48 h post-burn, at which point spleens were harvested. Histology was performed to localize splenic CD3 and measure the proportion of red and white pulp. Gene and protein expression was analyzed via qPCR, Western blot, and multiplex. The splenic artery diameter was maintained with water (-0.2 ± 0.32mm), limited-volume (0.36 ± 0.37mm), or volume-matched ORS (-0.2 ± 0.04mm), while no fluids led to a reduction (-0.97 ± 0.14mm) and IV fluids led to dilation (0.68 ± 0.30mm) 48 h post-burn. However, no differences in spleen wet-to-dry ratios were detected among treatments. Levels of white pulp were highest in the ad lib water group (233.0 ± 1.7AU), volume-matched ORS (229.7 ± 2.5), and IV groups (233.3 ± 1.363) compared to no fluids (221.9 ± 5.2) or low-volume ORS (218.7 ± 3.4). Gene expression of complement C5 and uteroglobin-related protein 2 were upregulated in IV animals by 2.76 and 2.43 fold, respectively, when compared to volume matched ORS. Protein expression of CD3 tended to be greatest in animals receiving ORS, and IV fluids. Protein levels of IL1ra were greatest in low and volume matched ORS compared to other groups. Burn injury leads to significant changes in splenic leukocytes, which can be altered with different resuscitation strategies. Specifically, access to enteral fluids preserves splenic lymphocytes post-burn similarly to IV fluids, and may uniquely alter the inflammatory response. Enteral fluids also maintain splenic perfusion, with minimal change in splenic artery diameter. The therapeutic efficacy of enteral resuscitation in burn injury warrants further investigation. Enteral fluids represent a viable means of maintaining splenic perfusion which could easily be used to buy time in mass casualty and prolonged field care scenarios in patients with no concomitant abdominal injuries.