In this clinically relevant, co-morbid, resuscitated large animal model of sepsis, we show (i) expression of OTR and GR in the porcine heart, (ii) a sepsis-induced loss of cardiac OTR and GR expression, coinciding with (iii) increased systemic troponin levels as a marker of cardiac injury, (iv) impaired GR signaling reflected in low levels of GR target genes, (v) increased levels of CSE and HIF1α mRNA, and (vi) a lower level of NRF2 mRNA, suggesting an impaired antioxidant defense. This evidence concerns the gene NFE2L2 and Sepsis.