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OBJECTIVES: Our objective was to describe the prevalence of urinary tract infection (UTI) and invasive bacterial infection (IBI) in febrile infants during the coronavirus disease 2019 pandemic. METHODS: We conducted a multicenter cross-sectional study that included 97 hospitals in the United States and Canada. We included full-term, well-appearing infants 8 to 60 days old with a temperature of ≥38°C and an emergency department visit or hospitalization at a participating site between November 1, 2020 and March 31, 2022. We used logistic regression to determine trends in the odds of an infant having UTI and IBI by study month and to determine the association of COVID-19 prevalence with the odds of an infant having UTI and IBI. RESULTS: We included 9112 infants; 603 (6.6%) had UTI, 163 (1.8%) had bacteremia without meningitis, and 43 (0.5%) had bacterial meningitis. UTI prevalence decreased from 11.2% in November 2020 to 3.0% in January 2022. IBI prevalence was highest in February 2021 (6.1%) and decreased to 0.4% in January 2022. There was a significant downward monthly trend for odds of UTI (odds ratio [OR] 0.93; 95% confidence interval [CI]: 0.91-0.94) and IBI (OR 0.90; 95% CI: 0.87-0.93). For every 5% increase in COVID-19 prevalence in the month of presentation, the odds of an infant having UTI (OR 0.97; 95% CI: 0.96-0.98) or bacteremia without meningitis decreased (OR 0.94; 95% CI: 0.88-0.99). CONCLUSIONS: The prevalence of UTI and IBI in eligible febrile infants decreased to previously published, prepandemic levels by early 2022. Higher monthly COVID-19 prevalence was associated with lower odds of UTI and bacteremia. [ABSTRACT FROM AUTHOR]