Introduction: Impacts of COVID-19 mitigation measures on seasonal respiratory viruses is unknown in sub-tropical climates. Methods: We compared weekly testing and test-positivity of respiratory infections in the 2019–2020 respiratory season to the 2012–2018 seasons in southern Puerto Rico using Wilcoxon signed rank tests. Results: Compared to the average for the 2012–2018 seasons, test-positivity was significantly lower for Influenza A (p<0.001) & B (p<0.001), respiratory syncytial virus (RSV) (p<0.01), respiratory adenovirus (AdV) (p<0.05), and other respiratory viruses (p<0.001) following March 2020 COVID-19 stay at home orders. Conclusions: Mitigation measures and behavioral social distancing choices may have reduced respiratory viral spread in southern Puerto Rico. [ABSTRACT FROM AUTHOR]