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The increasing concern about bacterial resistance has made the rational prescription of antibiotics even more urgent. The non-pharmacological measures established to reduce the impact of the SARS-CoV-2 pandemic have modified the epidemiology of pediatric infections and, consequently, the use of antibiotics. Interrupted time series (ITS) analyses are quasi-experimental studies that allow for the estimation of causal effects with observational data in “natural experiments”, such as changes in health policies or pandemics. The effect of the SARS-CoV-2 pandemic on the incidence of infectious diseases and the use of antibiotics between 2018 and 2020 in the Health Area of Vigo (Galicia, Spain) was quantified and analyzed. This paper outlines a real-world data study with administrative records from primary care services provided for the pediatric population. The records were related to episodes classified as infectious by the International Classification of Primary Care (ICPC-2) and oral medication in the therapeutic subgroup J01, corresponding to antibiotics for systemic use, according to the World Health Organization’s Anatomical Therapeutic Chemical (ATC) classification system. The records were classified according to incident episodes, age, dose per inhabitant, and year. Segmented regression models were applied using an algorithm that automatically identifies the number and position of the change points. During the SARS-CoV-2 pandemic, the number of infectious diseases being transmitted between individuals, through the air and through the fecal–oral route, significantly decreased, and a slight decrease in infections transmitted via other mechanisms (urinary tract infections) was also found. In parallel, during the months of the pandemic, there has been a marked and significant reduction in antibacterial agent utilization, mainly of penicillins, cephalosporins, and macrolides. ISCIII Network for Research on Chronicity, Primary Care, and Health Promotion | Ref. RD21/0016/0022