We proposed that decontamination of the digestive tract (SDD) initiated after experimental burn injury would decrease myocardial inflammation/dysfunction after a second insult such as septic challenge. Rats were divided into 8 experimental groups. Groups included sham burn + sham sepsis, burn alone, sepsis alone, and burn + sepsis given either water by oral gavage for 5 days after burn (or sham burn) or given oral antibiotics (polymyxin E, 15 mg; tobramycin, 6 mg; 5-flucytosin, 100 mg given by oral gavage, 2x/daily for 5 days after burn or sham burn). Cardiac function and inflammation were studied 24 hours after septic challenge. In the absence of SDD, burn alone, sepsis alone, or burn + septic challenge promoted cardiac myocyte secretion of TNF- (burn: 174±11; sepsis: 269±19; burn + sepsis: 453±14 pg/ml), IL-1: (burn: 35±2; sepsis: 29±1; burn + sepsis: 48±7 pg/ml), and IL-6 (burn: 143±18; sepsis: 116±3; burn + sepsis: 248±12) compared to values measured in sham (TNF-: 3±1; IL-1: 1±.4; IL-6: 6±1.5 pg/ml) (p<0.05). Impaired ventricular contraction/relaxation responses were evident in the absence of SDD (burn + sepsis: LVP, 65±4; +dP/dt, 1320±131 compared to values measured in shams: LVP 96±4, +dP/dt, 2095±99, p<0.05). SDD treatment of experimental burn attenuated septic challenge related inflammatory responses and improved myocardial contractile responses, producing cardiac TNF-, IL-1, and IL-6 levels, LVP, ±dP/dt values that were significantly better (p<0.05) than values measured in burn + sepsis in the absence of SDD. This work confirms that endogenous gut organisms contribute to sensitivity to subsequent infectious challenge.