Rationale: Hypercapnia has similar hemodynamic effects to those of a dobutamine infusion and may have relevance in the management of septic shock. Objectives: To compare the effects induced by hypercapnia to those of dobutamine in a clinically-relevant model of septic shock. Methods: Fecal peritonitis was induced in 21 anesthetized, invasively monitored, mechanically ventilated female sheep. A combination of Ringer's lactate and 6% hydroxyethyl starch solution was titrated to maintain constant cardiac filling throughout the experiments. Two hours after feces spillage, animals were randomized to one of three groups (each n=7): Hypercapnia: carbon dioxide given to maintain partial pressure of carbon dioxide between 55-65 mmHg throughout the experiment; Dobutamine: dobutamine infused intravenously (7 µg/kg/min); Control: no treatment. In the dobutamine and control groups, the partial pressure of carbon dioxide was kept between 35-45 mmHg. All animals were monitored until spontaneous death. Measurement and main results: The hypercapnia animals had significantly lower arterial pH than the other two groups (p<0.05). Hypercapnic and dobutamine-treated animals developed significantly higher heart rate, cardiac index, oxygen delivery and lower lactate concentrations than controls (p<0.05). Hypercapnic animals had lower postmortem lung wet/dry ratio than the control animals (p<0.05). The alveolar-arterial oxygen partial pressure difference and shunt fraction were significantly lower in hypercapnic animals than in the other groups (p<0.05). Conclusions: In this clinically relevant ovine model of septic shock, hypercapnia had similar effects to dobutamine on hemodynamic variables and lactic acidosis. Hypercapnia improved tissue oxygenation and reduced lung edema formation more than dobutamine administration.