Objective: Early management of trauma victims includes control of bleeding and rapid restoration of intravascular volume. However, it remains controversial whether infusion of blood products is superior to crystalloids alone. Therefore, it was the aim of the present study to determine whether resuscitation with red blood cells plus lactated Ringer's solution (RL) is more effective than RL alone in improving the cardiovascular and hepatocellular functions after trauma and severe hemorrhage. Design: Prospective study. Setting: Laboratory. Subjects: Sprague-Dawley rats. interventions and Measurements: Male adult rats were anesthetized and underwent a laparotomy to induce tissue trauma before hemorrhage. The animals were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximal bleed-out (MB) volume was returned in the form of RL, and were then resuscitated with either four times the volume of MB with RL or washed red blood cells (RBC) (~45% the volume of MB) in three times the volume of RL over 60 mins. Various in vivo heart performance variables, cardiac output, and hepatacellunar function (ie, the maximum velocity and the overall efficiency of indocyanine green clearance) were determined at 4 hrs after resuscitation. Hemoglobin, systemic oxygen delivery, circulating blood volume, and plasma levels of interleukin-6 were also measured. Main Results: At 4 hrs after RL resuscitation, heart performance, cardiac output and hepatocellular function were significantly depressed and plasma levels of interleukin-6 were significantly increased. Although infusion of RBC significantly increased mean arterial pressure, hemoglobin, and oxygen delivery compared with animals resuscitated with RL only, infusion of RBC did not further improve the depressed cardiovascular and hepatocellular functions under such conditions. Conclusion: Because infusion of RBC and RL resuscitation do not improve organ functions compared with RL resuscitation without RBC, it appears that pharmacologic agents in addition to fluid resuscitation are needed to restore cardiovascular and hepatacellular functions after trauma and hemorrhage.