Energy conversion schemes involving dihydrogen hold great potential for meeting sustainable energy needs, but widespread implementation cannot proceed without solutions that mitigate the cost of rare metal catalysts and the O2 instability of biological and bioinspired replacements. Recently, thick films (>100 μm) of redox polymers were shown to prevent O2 catalyst damage but also resulted in unnecessary catalyst load and mass transport limitations. Here we apply novel homogeneous thin films (down to 3 μm) that provide protection from O2 while achieving highly efficient catalyst utilization. Our empirical data are explained by modeling, demonstrating that resistance to O2 inactivation can be obtained for nonlimiting periods of time when the optimal thickness for catalyst utilization and current generation is achieved, even when using highly fragile catalysts such as the enzyme hydrogenase. We show that different protection mechanisms operate depending on the matrix dimensions and the intrinsic catalyst properties and can be integrated together synergistically to achieve stable H2 oxidation currents in the presence of O2, potentially enabling a plethora of practical applications for bioinspired catalysts under harsh oxidative conditions.