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Background: International travelers from regions with high incidence rates of COVID-19 have a high probability of being infected and spreading the disease when in contact with other people, so it is necessary to investigate the influence of the entry of these travelers on the transmission of COVID-19 during the second wave of the epidemic. Objective: To determine the influence of the entry of international travelers and other indicators on the transmission of COVID-19 in Santiago de Cuba province. Methods: an ecological study of correlation of the incidence of COVID-19 with certain variables was developed considering as units of analysis the municipalities of Santiago de Cuba province. Spearman's correlation coefficient was used to determine the correlation. To determine the variables that most influenced the number of confirmed cases, multiple linear regression and partial least squares were applied. Cluster analysis was used to determine the most similar municipalities. Results: six models and the formation of several clusters were obtained. The municipality of Santiago de Cuba was atypical. The most influential variables were: travelers, travelers with COVID, number of outbreaks, number of asymptomatic, population density and collaborator. The regions and countries that determined the model were America, Europe, Spain, Mexico and Venezuela. Conclusions: the number of travelers with and without COVID-19 has been a trigger for the number of infected cases in the epidemic in Santiago de Cuba. [ABSTRACT FROM AUTHOR]