Supercritical separation processes for a multi-component mixture of solutes are of practical interest. In this study, the experimental equilibrium solubilities of two solute mixtures, p-toluenesulfonamide ( p-TSA) and sulfanilamide (SNA), in supercritical carbon dioxide (SC CO 2) were measured at temperatures of 308, 318 and 328 K and pressures in the range of 11.0–21.0 MPa using a dynamic flow method. The effect of cosolvent on the multi-component system was investigated by the addition of a 3.5 mol% ethanol. In the ternary system ( p-TSA + SNA + CO 2), the solubility of SNA increased as compared to its binary system (SNA + CO 2), while the solubility of p-TSA decreased. In the quaternary system ( p-TSA + SNA + ethanol + CO 2), a significant solubility enhancement was observed for both p-TSA and SNA. The selectivity, which is thought to imply the intermolecular interactions between p-TSA and SNA, was also enhanced by the presence of ethanol so that the two solutes could be separated by a max. purity of 99.4%. The influence of the hydrogen bond interaction on solubility was discussed. The equations of Chrastil, Méndez-Santiago and Teja, and their modified forms were used to correlate the experimental data.