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 328K and pressures in the range of 11.0–21.0MPa using a dynamic flow method. The effect of cosolvent on the multi-component system was investigated by the addition of a 3.5mol% 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.