Dual-Energy Computed Tomography is of significant clinical interest due to the possibility of material differentiation and quantification. In current clinical routine, primarily two materials are differentiated, e.g., iodine and soft-tissue. A ventilation-perfusion-examination acquired within a single CT scan requires two contrast agents, e.g., xenon and gadolinium, and a three-material differentiation. In the current study, we have developed a solution for three-material differentiation for a ventilation-perfusion-examination. A landrace pig was examined using a dual-layer CT, and three scans were performed: (1) native; (2) xenon ventilation only; (3) xenon ventilation and gadolinium perfusion. An in-house developed algorithm was used to obtain xenon- and gadolinium-density maps. Firstly, lung tissue was segmented from other tissue. Consequently, a two-material decomposition was performed for lung tissue (xenon/soft-tissue) and for remaining tissue (gadolinium/soft-tissue). Results reveal that it was possible to differentiate xenon and gadolinium in a ventilation/perfusion scan of a pig, resulting in xenon and gadolinium density maps. By summation of both density maps, a three-material differentiation (xenon/gadolinium/soft tissue) can be performed and thus, xenon ventilation and gadolinium perfusion can be visualized in a single CT scan. In an additionally performed phantom study, xenon and gadolinium quantification showed very accurate results (r > 0.999 between measured and known concentrations).