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Social distancing (SD) during the coronavirus disease 2019 (COVID-19) pandemic has largely removed children from school, day care, and other contact with peers. In addition to reducing transmission of severe acute respiratory syndrome coronavirus 2, these changes would be expected to reduce the transmission of other infectious diseases among children. We sought to determine the effect of SD on 12 infectious diseases commonly diagnosed in pediatric primary care that are contagious to various extents: acute otitis media (AOM), bronchiolitis, common cold, croup, gastroenteritis, influenza, nonstreptococcal pharyngitis, pneumonia, sinusitis, skin and soft tissue infections (SSTIs), streptococcal pharyngitis, and urinary tract infection (UTI).Using electronic health record data from a large Massachusetts pediatric primary care network that cares for ∼375 000 children, we analyzed the weekly incidence of each diagnosis from weekday in-person and telemedicine encounters (excluding holidays) for children age 0 to 17 years of age for the same calendar period in 2019 and 2020 starting from January 1. We defined the pre-SD period as calendar weeks 1 to 9 of each respective year; allowed for a 3-week implementation period as SD was enacted in 2020 (statewide state of emergency declared in week 10, school and nonessential businesses closed in week 11, and stay-at-home advisory issued in week 12); and defined the post-SD period as calendar weeks 13 to 18, the most recent data available for analysis. To isolate the effect of SD, we performed a difference-in-differences regression analysis1 using a multivariable Poisson regression model with diagnosis count as a function of calendar year, time period (pre-SD versus post-SD), and the interaction between the two.The diagnosis rates per 100 000 patients for each time period and the difference-in-differences analysis for 2020 vs 2019 are displayed in Table 1 and Fig 1. The prevalence of each condition was significantly lower in the 2020 post-SD period than would be expected for all conditions analyzed (P < .001 for all diagnoses).SD policies enacted in Massachusetts to mitigate the COVID-19 pandemic resulted in a profound decrease in the diagnosis of common infectious diseases among children. This reduction could be due to 1, or both, of 2 factors: a decline in the prevalence of the conditions or a choice not to seek care when the conditions occurred.2 The smaller decrease in diagnoses for UTI, an infectious but not generally not contagious disease, suggests that changes in care-seeking behavior had a relatively modest effect on the other observed declines.Although it is not surprising that the transmission of infectious diseases decreased with SD, these data demonstrate the extent to which transmission of common pediatric infections can be altered when close contact with other children is eliminated. Notably, 3 of the studied diseases, namely, influenza, croup, and bronchiolitis, essentially disappeared with SD.The trajectory of influenza is especially interesting. Diagnoses in 2020 exceeded those in 2019 as expected from national surveillance data,3 but the spread of influenza appears to have ended abruptly with SD. This finding differs somewhat from a recent report from Japan revealing a significant but not as dramatic decline in influenza cases coincident with SD in that country.4 The differing results may relate to the timing of SD within the influenza season, different approaches to SD in the 2 locations, or the fact that the Japanese study included patients of all ages, whereas ours is focused only on children.The infectious disease risks of contact with others have always been implicitly weighed against the benefits of social interaction. The current natural experiment of abrupt, widespread SD during the COVID-19 pandemic has allowed for a more explicit appreciation of the magnitude of these risks in children and may inform strategies for infectious disease risk mitigation as social interaction increases in the future.