Objectives There was an overall decline in pediatric emergency department visits during the COVID-19 pandemic. Caregivers are educated to bring febrile neonates promptly to the emergency department; however, for infants aged 29 to 60 days, there may not be the same urgency especially during a pandemic. There may have been a resultant change in the clinical and laboratory high-risk markers and infection rates in this patient population during the pandemic. Methods This was a single-center retrospective cohort study of infants aged 29 to 60 days presenting to the emergency department of an urban tertiary care children's hospital because of fever (>38°C) between March 11 and December 31, 2020, compared with those presenting in the same period during the 3 prior years (2017 through 2019). Patients were categorized as having high-risk criteria on a predetermined definition of ill appearance, white blood cell count, and urinalysis based on our hospital's evidence-based pathway. Information on infection type was also collected. Results A total of 251 patients were included in the final analysis. Comparison of the prepandemic and pandemic cohorts showed a significant increase in the proportion of patients with urinary tract infections (P = 0.017) and bacteremia (P = 0.02) and those presenting with high-risk white blood cell count (P = 0.028) and urinalysis (P = 0.034). There was no significant difference in patient demographics or in high-risk ill appearance (P = 0.208). Conclusions This study demonstrates a significant increase in the rates of urinary tract infection and bacteremia in addition to the objective markers used to risk-stratify febrile infants aged 29 to 60 days. This supports the need for attentiveness in evaluating these febrile infants in the emergency department.