In Spring 2020, the first wave of the COVID-19 pandemic hit Europe most severely. While empirical evidence regarding the economic costs of the strict lockdown measures enacted during the periods before the widespread diffusion of vaccines is now available, little is known about the economic impact of both strict lockdowns and partial closures on border regions. This is instead a relevant case study to analyze, in particular in the light of the asymmetric nature of border closures. This paper fills this gap and offers two sets of analyses: a first assessment of partial closures, enacted after the first wave of the COVID-19 pandemic and based on the approach applied to European cross-border regions to measure the costs of legal and administrative barriers (Camagni et al., 2019); and a second measurement based on simulating the impacts of full closures with the Macroeconometric Social Sectoral Territorial (MASST)-4 model (Capello & Caragliu, 2021a). These analyses also allow for the pinpointing of the spatial distribution of economic losses, and to identify whether different regional typologies suffered the highest contraction.