Treatment with oxygen exerts beneficial effects and prolongs survival in hemorrhagic shock induced by controlled bleeding. We evaluated the effects of inhalation of 100% oxygen in four models of uncontrolled bleeding in rats: amputation of the tail, laceration of two branches of the ileocolic artery, incision of the spleen, and laceration of the lateral lobe of the liver. After tail amputation, oxygen caused a short and transient increase in mean arterial blood pressure (MABP; P < 0.01), decreased distal aorta (DA) blood flow by 27% (P < 0.01), and induced transient redistribution of blood flow to the superior mesenteric artery (SMA; P < 0.01). Later on, MABP in the oxygen group decreased gradually and was significantly lower than in air controls (P < 0.01). Oxygen therapy increased the mean blood loss by 40% (P < 0.01), increased blood lactate (P < 0.01), and shortened the survival time (P < 0.01). After laceration of two branches of the ileocolic artery, oxygen treatment caused a transient increase in MABP and redistribution of blood flow to the SMA that was followed by a comparable decrease in MABP, increase in vascular resistance, and decreased blood flow in the DA and SMA. In this model, oxygen did not affect bleeding volume, blood lactate, or survival. A similar transient regional hemodynamic effect was found when oxygen was administered after spleen or liver injury; however, in both models, oxygen maintained MABP at significantly higher values (P < 0.05). The results point to differential effects of oxygen in uncontrolled bleeding with benefits in bleeding from small parenchymal vessels and possible detrimental effect in bleeding from large size vessels.