The methodology used for calculating the physical exergy and the chemical exergy of mixtures of crude oils and their fractions is presented in this paper, using computer programs coupled with the AspenPlus simulation code. First, the procedure for the detailed characterization of a crude oil mixture is described, based on the results of experimental assays. After that, the steps required to determine the reference conditions needed for the calculation of the physical exergy are presented, and the sequence by which these values are retrieved from a simulation run is explained, in order to be used in a fortran computer program. Finally, from the mixture characterization, the procedure for determining the chemical exergy of each component (identified components and pseudo-components) of the mixture is presented, in order to add it to the physical exergy to obtain the total exergy of the mixture stream. The methodology is illustrated with a mixture of Mexican Maya and Isthmus crude oils, and its application to the analysis of a crude oil combined distillation unit is presented in this paper. This paper was presented at the ECOS’98 Conference in Nancy, June 8-10, 1998