The in-plane effective diffusion coefficients in gas diffusion layers typically used in fuel cell electrodes were measured as a function of compression and hydrophobic polymer loading. This method was based on the transient diffusion of oxygen from air into an initially nitrogen purged porous sample and has proven to be accurate, fast, and straightforward. As anticipated, with higher compressions and higher PTFE loadings, effective diffusivity decreased, as a result of less pore space available for transport and because tortuosity increased. When plotted against compressed porosity, the effective diffusivity of untreated and treated materials for a given type of sample collapsed on top of each other, despite the simultaneous impact of PTFE loading and compression. It was possible to distinguish between the impact of PTFE and compression by plotting the data as tortuosity against compressed thickness. High compressions on the sample lead to irreversible damages to the fiber structure, resulting in decreased or unexpectedly low tortuosity. Finally, a percolation model was fitted through one of the tested materials and a reasonable agreement was observed for lower compression, but a fit to the entire data could not be achieved. This was attributed to fundamental structural changes occurring in the sample upon high compressions, an observation that helps to explain the general inability of theoretical tortuosity models to describe GDLs.