This article quantifies the spatial diffusion capacity –spatial spillover effect– of the COVID-19 virus at municipal level for the department of Antioquia, Colombia, from the onset of its spread in 2020 until December 2021. To this end, error and spatial lag models were implemented to identify the pattern of infections and classify municipalities in terms of their diffusion capacity. The empirical results show a characteristic spatial pattern conditioned by the distribution of economic activity. There is also evidence indicating a reduction of about 83% in the average diffusion capacity of the virus associated with the vaccination process implemented in the department. The findings are valuable for informing public policies that encompass the geographic environment and are necessary for mitigating viruses and similar pandemic processes.