Positron annihilation depth-profiling is used as an innovative tool to monitor the evolution of vacancy defects in two series of ZnO:Al transparent conductive oxide (TCO) layers for Cu(In,Ga)Se2 (CIGS) solar cells under accelerated degradation at 85??C/85% relative humidity. The first series of ZnO:Al layers are deposited directly on flat glass substrates, leading to low densities of (extended) grain boundaries in the ZnO:Al. These ZnO:Al layers only show an increase in open volume upon degradation in the near-surface range. The second series of ZnO:Al layers are deposited on the more corrugated surface of CdS/CIGS/Mo solar cells, and show, on the other hand, a pronounced formation of open volume throughout the layer. Its depth-dependence is consistent with in-diffusion of molecules such as H2O and CO2 into the ZnO:Al layer via the grain boundaries, as primary driver for the degradation. The detected time-dependence of the growth of open volume at the grain boundaries in the ZnO:Al TCO layer matches the time scale of the observed reduction in solar cell efficiency and series resistance, suggesting that the generated open volume induces a significant barrier against charge carrier transport.@en