Although the mouse has been extensively used to study immune consequences of sepsis and other genetic anomalies, the changes in various cardiovascular parameters such as cardiac output, organ perfusion, as well as oxygen utilization have not been characterized in this species during sepsis. To determine this, polymicrobial sepsis was induced in male adult C3H/NeN mice by cecal ligation and puncture (CLP, two punctures with a 22-gauge needle). The animals were then resuscitated with normal saline subcutaneously. At 5 or 24 h after CLP (time points previously shown to be within the hyperdynamic and hypodynamic stage of sepsis, respectively, in the rat), cardiac output and blood flow in major organs were determined using a well-established radioactive microsphere method, and stroke volume and total peripheral resistance were calculated. In addition, oxygen delivery and consumption were determined. The results indicate that cardiac output, stroke volume, oxygen delivery and consumption, and blood flow in the liver, small intestine, spleen, and kidneys increased significantly at 5 h after CLP. This was associated with significantly decreased total peripheral resistance. In contrast, total peripheral resistance increased and the other above-mentioned parameters, as well as mean arterial pressure, decreased significantly at 24 h after the onset of sepsis. Thus, the cardiovascular response to polymicrobial sepsis in the mouse is characterized by an early hyperdynamic phase (i.e., 5 h after CLP) followed by a late hypodynamic phase (24 h post-CLP). Since the radioactive microsphere technique provides a reliable method for determining various hemodynamic parameters in the mouse, the correlation between the cardiovascular response and immune or potentially genetic alterations can be examined in this species during the progression of sepsis.