This article aims to develop an entropy based method of systematically improving efficiency of fuel cells. Entropy production of both electrochemical and thermofluid irreversibilities is formulated based on the Second Law. Ohmic, concentration, and activation irreversibilities occur within the electrodes, while thermal and friction irreversibilities occur within the fuel channel. These irreversibilities reduce the overall cell efficiency by generating voltage losses. Unlike past studies, this article considers fuel channel irreversibilities within the total entropy production, for both solid oxide fuel cells (SOFCs) and proton exchange membrane fuel cells (PEMFCs). Predicted results of entropy production are shown at varying operating temperatures, surface resistances, and channel configurations. Numerical predictions are compared successfully against past measured data of voltage profiles, thereby providing useful validation of the entropy based formulation. The Second Law stipulates the maximum theoretical capability of energy conversion within the fuel cell. Unlike past methods characterizing voltage losses through overpotential or polarization curves, the entropy based method provides a useful alternative and systematic procedure for reducing voltage losses.