Background: The impact of public health interventions against the coronavirus disease 2019 (COVID-19) pandemic on the occurrence of Enterobacterales outbreaks in hospitals remains unclear. Objective: To determine the effect of the COVID-19 national health alert on the secular trend of Enterobacterales outbreaks in Chilean public hospitals while characterizing their antibiotic resistance patterns. Methods: Nationwide retrospective ecological study using interrupted time series analysis of monthly outbreak-related cases over three periods: pre-pandemic (January 2017–February 2020), national health alert (March 2020–August 2023), and post-pandemic (September–December 2023). Results: A total of 106 outbreaks, 1131 associated cases and 254 deaths were identified in 47/196 (24.0%) hospitals. Cases increased gradually [0.39 cases/month, 95% confidence interval (CI) 0.02–0.75; P=0.040] in the pre-pandemic years. A sudden increase of 33.42 cases (95% CI 7.53–59.31; P=0.012) occurred in March 2020, followed by a gradual decrease (1.28 cases/month, 95% CI 0.38–2.17; P=0.006) during the national health alert period. An increase of 18.02 cases (95% CI 2.89–33.15; P=0.020) occurred in September 2023, and preceded a gradual post-pandemic decline (6.21 cases/month, 95% CI 1.11–11.31; P=0.018). The prevalence of cases caused by carbapenemase-producing Enterobacterales increased significantly (P<0.001) during (79.9%) and after (100.0%) the national health alert period compared with the pre-pandemic period (35.3%). Conclusions: The COVID-19 national health alert was associated with significant shifts in the secular trend of cases associated with Enterobacterales outbreaks in Chilean public hospitals, including abrupt increases at the beginning and end of the national health alert period, and gradual decreases during and after this period. A sharp increase in carbapenemase production was observed across outbreaks after the onset of the COVID-19 pandemic.