Oxygen delivery and consumption after hemodilution with a perfluorocarbon based oxygen carrier (PFCOC) was evaluated at sea level and at 2600m above sea level. Fifteen anesthetized rats were subjected to a two-exchange normovolemic hemodilution of 40% of the circulating blood volume each. First exchange was performed with a colloid solution. Second exchange with 80% PFC oxygen carrier and 20% colloid. Animals were then ventilated with 100% oxygen. Experiments were performed at barometric pressure of 1.0 atm (Sea Level group, n = 9) or 0.74 atm (2600m group, n = 6). Blood gases, hematocrit, fluorocrit and hemoglobin content were measured at baseline, and 15 min after each exchange. After hemodilution, total arterial content was not modified by the PFCOC in either group. In contrast, arteriovenous oxygen difference (CavO₂) increased significantly in both groups as did the oxygen extraction ratio. In the second exchange, although total arterial content was similar between the two groups, the PFC and plasma phases contributed significantly more at sea level. CavO₂ was significantly less at sea level with a higher contribution from the PFC and plasma phases. In conclusion, hemodilution with a PFCOC induced changes in oxygen delivery and consumption that differ with altitude. The 2600m group exhibited a higher oxygen extraction ratio and arteriovenous oxygen difference, with reduced oxygen delivery and unloading from both the fluorocarbon and plasma phase. Therefore, the efficacy of PFCOCs at 2600m above sea level is reduced, and altitude must be taken into account when using PFCOCs.