The impact of various Lewis bases on the miscibility of siloxane polymers in CO2 was investigated using both ab initio calculations and experimental phase behavior studies. A series of side-chain functional silicones were synthesized containing various Lewis bases in the side chain, and their phase behavior was compared in CO2 at 295 K. Calculations showed that interactions between CO2 and ethers (either a dialkyl ether or the ether oxygen in an ester group) should be as favorable as interactions between CO2 and a carbonyl oxygen. Indeed, phase behavior results seemed to support this, as ether-functional silicones exhibited miscibility pressures as low or lower than acetate-functional analogues. Further, a keto-functional material was not nearly as CO2-philic as the acetate functional analogue. In general, the location of the phase boundary in CO2 is governed by a balance between forces working to increase miscibility pressures, such as increased cohesive energy density of the polymer or factors suppressing the entropy of mixing, and those working to lower miscibility pressures, such as enhanced specific interactions with CO2 and increased free volume or chain flexibility.