The optimization of the composition of mixed surfactants used as micellar electrokinetic chromatography (MEKC) pseudostationary phases is proposed as an effective method for the separation of complex mixtures of analytes. The solvation parameter model is used to select two surfactants (lithium dodecyl sulfate, LDS, and lithium perfluorooctanesulfonate, LPFOS) with contrasting solvation properties. Combination of these two surfactants allows variations of the solvation properties of MEKC pseudostationary phase along a wide range. Thus, the convenient variation of the proportion of both surfactants allows an effective control of the selectivity in such systems. An algorithm that predicts the overall resolution of a given mixture of compounds is described and applied to optimize the composition of the mixed surfactant for the separation of the mixture. The algorithm is based on the calculation of peak purities on simulated chromatograms as a function of the composition of the mixed LDS/LPFOS micellar buffer from data at several micellar buffer compositions. Successful separations were achieved for mixtures containing up to 20 compounds, in less than 12 min.