To our knowledge, this is the first study providing evidence that, under conditions with high endogenous AVP plasma levels, first-line treatment with the selective V2R-antagonist supplemented with open-label norepinephrine improves cardiovascular, metabolic, liver, and renal function and slightly prolongs survival when compared with first-line therapy with AVP or placebo in ovine septic shock. This evidence concerns the gene AVPR2 and septic shock.