The determination of oxygen consumption using arterio-venous oxygen content differences is dependent on accurate oxyhemoglobin saturation measurements. Because swine are a common experimental species, we describe the validation of co-oximeter for porcine specific oxyhemoglobin saturation. After developing a non-linear mathematical model of the porcine oxyhemoglobin saturation curve, 366 porcine oxyhemoglobin saturation determinations were made with a calibrated blood gas analyzer and a porcine specific co-oximeter. There was a high degree of correlation with minimal variability (r² = 0.99, SEest = 5.2%) between the mathematical model and the porcine specific co-oximeter measurements. Bland-Altman comparison showed that the co-oximeter measurements were biased slightly lower (-0.4 vol%) and the limits of agreement (± 2SD) were 0.7 and -1.5 vol%. This is in contrast to a 10-20 vol% error if human specific methods were used. The results show excellent agreement between the nonlinear model and co-oximeter for porcine specific oxyhemoglobin saturation measurements. In contrast, comparison of the porcine specific oxyhemoglobin saturations with saturations obtained using human methods highlights the necessity of species-specific measurement methodology.