Cosolvents exhibit significant effects on the partitioning behavior of dilute solutes between a supercritical CO2 fluid phase and cross-linked siloxane-based polymers. A spectroscopic technique was developed and applied that allows us to measure the partition coefficients of both the cosolvents and solutes between the two phases. The Sanchez-Lacombe lattice fluid equation of state was extended to represent a two-phase, four-component system and was quantitatively successful in representing the volumetric and phase-equilibria properties of such systems. We then apply the model and our data to investigate the magnitudes of stationary-phase effects in supercritical fluid chromatography and explore opportunities to use the model for a priori prediction of separation.