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Abstract Background A unique policy of perimeter closures of Basic Health Zones (small administrative health units) was implemented in the Autonomous Community of Madrid from September 21st 2020 to May 23rd 2021 to face the COVID-19 pandemic. Aim To assess the impact of local perimeter confinements on the 14-days cumulative incidence of SARS-CoV-2 during the second wave of the pandemic in Madrid, Spain. Methods We compare the errors in estimation of two families of mathematical models: ones that include the perimeter closures as explanatory covariables and ones that do not, in search of a significant improvement in estimation of one family over the other. We incorporate leave-one-out cross-validation, and at each step of this process we select the best model in AIC score from a family of 15 differently tuned ones. Results The two families of models provided very similar estimations, for a 1- to 3-weeks delay in observed cumulative incidence, and also when restricting the analysis to only those Basic Health Zones that were subject to at least one closure during the time under study. In all cases the correlation between the errors yielded by both families of models was higher than 0.98 (±10− 3 95% CI), and the average difference of estimated 14-days cumulative incidence was smaller than 1.49 (±0.33 95% CI). Conclusion Our analysis suggests that the perimeter closures by Basic Health Zone did not have a significant effect on the epidemic curve in Madrid.