Objectives We examine the option to operate fuel cells, in particular solid oxide fuel cells (SOFCs), on a mixture of fuel with air and apply the same mixture to both the anode and cathode. This kind of cell is referred to as a mixed-reactant fuel-cell (MR-FC or MR-SOFC). Operating a fuel cell on a uniform mixture of the reactants allows significant changes in the cell design having, potentially, higher power density and higher fuel utilization as well as enabling the use of porous electrolyte thin layers and lowering production costs. To achieve this the symmetry has to be broken by using different materials as catalysts for the anode and cathode. The primary challenge is selectivity, allowing the anode only fuel oxidation by oxygen ions emerging from the solid electrolyte and the cathode only oxygen reduction while all materials in the cell should not catalyze the direct chemical reaction within the mixture. The aim is to discuss potential ways to achieve that selectivity and test it. Selectivity is in particular a challenge in MR- SOFCs as they should operate at elevated temperature where many reactions are active and selectivity is difficult to be achieved. New results Selectivity can be controlled by materials properties, cell design in particular the electrode design and operation conditions.1 The following material properties affect selectivity: the work function, electron energy levels and energy band banding at the surface, point defects, in particular in the surface layer, generation of local electrical fields by surface additives and tendency towards reduction of the oxides in the cell which serve as the electrolyte, electrodes and possibly also as the interconnects and current collectors. Proper electrode design can enhance selectivity taking advantage of the different diffusion coefficients and concentration gradients in the gas components i.e. fuel, oxygen and reaction product. Working conditions that can contribute to selectivity are: temperature, flow rate hence residence time in the hot zone and electrical current drawn from the cell as it affects the concentration gradients in the gas phase at the electrodes. These factors apply to all mixed reactant fuel cells and allow to enhance selectivity in them. They are crucial for the high temperature MR-SOFCs. Test design is discussed suggesting that first each material is tested separately to screen those that enhance the forbidden chemical reaction within the gas mixture. Preliminary experimental results are reported. The procedure suggested to test selectivity and cell performance is discussed. Moderately diluted hydrogen can be used as the fuel in the mixture, as found experimentally contrary to common believe, despite the high temperatures used (600°C) as long as no catalyst is present. It is emphasized that single chamber SOFC reported so far are not true MR-SOFCs as one of the electrode is not selective. Significance Determining the catalytic properties of materials, in the present case those relevant to solid oxide fuel cells, is of general interest and importance. Achieving selectivity will provide the basic necessary condition for the construction of mixed reactant solid oxide fuel cells. Once this is achieved accelerating reaction rates will be the next challenge. Acknowledgement This research was supported by Israel Science Foundation ISF under grant No. 699/11. References I. Riess, Funct. Mater. Lett. 8 1540010 (2015).