Positron annihilation lifetime spectroscopy (PALS) and Doppler broadening positron annihilation spectroscopy DB-PAS) depth profiling demonstrate pronounced growth of vacancy clusters at the grain boundaries of as-deposited Al-doped ZnO films deposited as transparent conductive oxide (TCO) on Cu(In, Ga)Se2 (CIGS) solar cells upon accelerated degradation at 85 ◦C/85% relative humidity. Quantitative fractions of positrons trapped either in the vacancy clusters at the grain boundaries or in Zn monovacancies inside the grains of ZnO:Al were obtained by detailed analysis of the PALS data using a positron trapping model. The time and depth dependence of the positron Doppler depth profiles can be accurately described using a planar diffusion model, with an extracted diffusion coefficient of 35 nm2/hour characteristic for in-diffusion of molecules such as H2O andCO2 into ZnO:Al TCO films via the grain boundaries, where they react with the ZnO:Al. This leads to increased open volume at the grain boundaries that imposes additional transport barriers and may lead to charge carrier trapping and nonradiative recombination. Simultaneously, a pronounced increase in series resistance and a strong reduction in efficiency of the ZnO:Al capped CIGS solar cells is observed on a remarkably similar timescale. This strongly indicates that these atomic-scale processes of molecular in-diffusion and creation of open volume at the grain boundaries play a key role in the degradation of the solar cells. PhySH: Solar Cells, Positron Annihilation Spectroscopy, Grain Boundaries, Vacancies, Thin Films, Diffusion, Electrical Properties, Solid State Chemistry, Optoelectronics@en