A Variable-Resolution, global configuration of the Community Earth System Model (VR-CESM) in which the atmosphere and land are the only active components is employed to investigate the climate of the Euro-Mediterranean region. Two variable-resolution grids with regionally-refined resolutions of 0.25° and 0.125° over the study domain, respectively, are used. The fidelity of these VR-CESM simulations is evaluated considering the near-surface air temperature and precipitation fields for the 2000-2014 period in comparison to available observation-based datasets and those of a coarse resolution (quasi-uniform 1°) control simulation. Our analysis shows that, as a global model, VR-CESM is a promising alternative to regional climate models to advance our understanding of the Euro-Mediterranean climate. The improvements obtained are mainly related to a better representation of the complex topography of the region with higher resolution. Increasing the regional resolution to 0.25° generally yields considerable improvements over the control simulation, however some persistent biases remain. Doubling the highest resolution to 0.125° leads to only modest improvements, primarily in the representation of small-scale processes including representation of extreme events that are of substantial relevance for the present and future of the regional climate.