In this study, multidisciplinary approaches to optimizing serpentine gas flow channels stamped on sheet metal with various design parameters (i.e., channel-to-rib width ratio, draft angle, inner fillet radius, and channel depth) are implemented to identify the fluid-structure interaction characteristics of locally deformed gas diffusion media (GDM) and the rate of entropy generation for bypass flow through the porous GDM. First, static structural analysis is conducted to demonstrate the GDM deformation by stack compression and its mechanical effects on fluidic properties of GDM experimentally and numerically. The GDM-channel model results agree with the experimental results within a maximum error of less than 10%. Emphasis is placed on understanding how the reactant gas flow through GDM effectively transports the oxygen gas to catalyst layers. Next, parametric studies are conducted to identify the dominant design effects on the fluidic performance over the entire computational domain. Subsequently, a design optimization method is applied to obtain the most favorable flow channel designs with trapezoidal cross-sections. In the optimized serpentine channel design, the maximized oxygen transport ratio is predicted to be 0.718 at the interface between the GDM and catalyst layers under the constraint of total pressure drop. (C) 2016 Elsevier Ltd. All rights reserved.