To evaluate a perfluorocarbon based oxygen carrier (Oxyfluor), a porcine model of cardiopulmonary bypass (CPB) was implemented. Swine (30 kg) were subjected to 2 h of normothermic CPB using Oxyfluor (OF group, n = 8) or Ringer's lactate (RL group, n = 13) as the prime. Mean arterial pressure (MAP) was kept at 50 mm Hg, flow rate at 80 ml x min(-1) x kg(-1), and PaCO2 at 35 mm Hg. Hemodynamic, hematologic, fluid balance, and blood gasimetry variables were measured. Total body oxygen delivery (DO2), consumption (VO2), and the fractional contribution to delivery (FCD) and to consumption (FCC) of the red blood cells (RBC), PFC, and plasma phases were calculated. Mixed venous PO2 (PvO2) was significantly higher at 30 min and 1 h on CPB in the OF group than in the RL group. FCCRBC was significantly lower at 30 min, 1 h, and 90 min on CPB in the OF group than in the RL group. PvjO2, Ca-vO2, Ca-vj O2, and VO2 were slightly higher in the OF group than in the RL group. Tissue fluid accumulation was not alleviated with Oxyfluor, and tissue and brain acidosis were significantly increased in the OF group. This study presented evidence that Oxyfluor improved tissue oxygenation and total body oxygen consumption during experimental CPB. In addition, Oxyfluor reduced FCCRBC, increasing oxygen transport reserve of the RBC phase, which can be useful to reduce hypoxic events during CPB. Further research should be conducted to optimize PFC-OCs for use in CPB and to reduce secondary effects.