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The COVID-19 pandemic underscored the critical need to strengthen healthcare systems and optimize resource allocation planning during times of disruption and crisis. This retrospective, single-center, cross-sectional study included 33,158 admissions for patients ≤ 17 years old admitted to the Children's Hospital (CH) between January 1, 2017, and December 31, 2021. Data was abstracted using Vizient Clinical Data Base and the internal data warehouse. A Poisson regression model was implemented to compare admission diagnosis patterns during the pre- and intra-pandemic phases. CH SARS-CoV-2 prevalence rate was 0.1% in 2020 and 0.5% in 2021. There was a decrease in overall admissions to the CH (p < 0.01) and PICU (p < 0.01) at the onset of the pandemic. There were significant and variable differences in admission patterns for certain infectious and seizure-related diagnoses. The CH experienced an increase in certain specific mental health diagnoses. Seasonality was noted for viral bronchiolitis during the pre-pandemic phase, but was disrupted during the intra-pandemic phase. The COVID-19 pandemic had a significant impact on the number and pattern of admissions, despite low prevalence of SARS-CoV-2 in our hospital. These changes may be secondary to COVID-19 community mitigation strategies. Results can inform anticipated patterns during future pandemics.