Plasticity and asperity-induced crack closure under mixed-mode non-proportional loading are investigated, using numerical models. It is shown that the applied mode II can either increase or decrease the effective DKI, depending on the R ratio and loading path. In some cases, mode II is found to have opposite effects on each of the two closure mechanisms. These results are coherent with some crack-length or roughness-dependent variations in mode I fatigue crack growth rate due to the presence of a static mode II reported in the literature. For 90 out-of-phase mixed-mode loading, mode II is predicted to reduce drastically or even suppress plasticity-induced closure.