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There is a considerable burden of children being hospitalized due to infectious diseases worldwide. The COVID-19 pandemic provided a unique opportunity to examine effects of worldwide efforts to control spread of infection. We aimed to investigate overall age-specific hospitalizations due to viral and bacterial infections and diseases triggered by respiratory tract infections during and after lockdown. This nationwide register-based observational study included children from 29 days to 17 years old hospitalized in all Danish pediatric emergency departments during the years 2015-2021. Main outcomes were ICD-10 diagnoses for infectious diseases and infection triggered illnesses. Fluctuations in hospitalization events were explored using figures with weekly events per 100,000. Total events followed a predictable pattern during 2015-2019. In 2020-2021, there was a drop in hospital encounters after lockdowns and surge after reopenings. In 2021, there was a surge of hospital encounters in the late summer due to respiratory syncytial virus infections and asthmatic bronchitis mostly in infants from 29 days to 2 years. For the infectious diseases, there was a dramatic decrease in events after lockdowns and immediate increase in cases that followed the same pattern of previous years after reopenings. Bacterial infections, like urinary tract infections, sepsis, and meningitis followed a steady pattern throughout all calendar-years.CONCLUSIONS: Nationwide efforts to minimize infectious disease spread like lockdowns have a preventative and period lasting effect but reopenings/reunions result in surges of infectious diseases. This might be due to children not getting immunized steadily thereby increasing the pool of possible hosts for potential viral infections.WHAT IS KNOWN: • There is a seasonal fluctuation in viral/respiratory infections in children with higher infection rates in the winter and lower rates in the summer. • RSV infection is a major source of concern.WHAT IS NEW: • Major lockdowns and reopenings disrupt the seasonal fluctuations which can result in high surges in infections that increases the burden of children emergency departments and the risk of serious complications.

It remains unknown how Coronavirus disease-2019 (COVID-19) prevention measures implemented on March 12, 2020, have affected the rate of pediatric infection-related hospitalizations in Denmark. Therefore, we investigated the rate of pediatric infection–related hospitalizations during the COVID-19 pandemic. We used a retrospective cohort design and included all Danish children < 18 years. Infection-related hospitalizations were assessed during study periods in 2020 vs. 2018/2019, and we computed incidence rate ratios (IRRs) with 95% confidence intervals (CIs) using Poisson regression. In the 2020 study period, 3093 children were hospitalized with an infection, while the corresponding figures for 2018 and 2019 study periods were 4824 and 3830, respectively. When comparing the 2020 to the 2018/2019 study period prior to nationwide lockdown, we observed a decline in infection-related hospitalizations (12.68 (95% CI, 12.22–13.16) vs. 15.49 (95% CI, 15.12–15.86) per 1000 person-years). We further observed decreased IRRs, especially during the lockdown period (week 11: 0.64 (95% CI, 0.55–0.75); week 12: 0.26 (95% CI, 0.21–0.33); week 13: 0.13 (95% CI, 0.10–0.19)). Conclusion: The rate of pediatric infection-related hospitalizations in Denmark declined during the COVID-19 pandemic in 2020 compared to that in 2018/2019, with a 36% decline during initiation of the nationwide lockdown period.What is Known:• Due to the COVID-19 pandemic, several countries have implemented mitigation strategies such as lockdown of non-critical business functions. Most of these strategies have previously been proven effective on interruption of infection transmission.• It remains unclear how the mitigation strategies have affected the rate of pediatric infection–related hospitalizations.What is New:• Insight on how COVID-19 prevention measures have affected the frequency of infection-related hospitalization.• Valuable knowledge on how to act in potential future pandemics. Supplementary Information The online version contains supplementary material available at 10.1007/s00431-021-03934-2.