OBJECTIVE: To determine features that distinguish febrile young infants with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: Retrospective single-center study included febrile infants <57 days of age evaluated in the emergency department of Cohen Children's Medical Center of Northwell Health, New Hyde Park, New York, from March 1 to April 30 of 2018, 2019, and 2020. Sociodemographic and clinical features were compared between those seen during the 2020 coronavirus disease-2019 pandemic and previous years, as well as between infants with SARS-CoV-2 infection and infants without SARS-CoV-2 infection (SARS-CoV-2 negative or evaluated during 2018 and 2019). RESULTS: In all, 124 febrile infants <57 days of age were identified; 38 during the 2-month study period in 2018, 33 in 2019, and 53 in 2020. During 2020, fewer febrile infants had a serious bacterial infection or a positive respiratory viral panel than in prior years (6% vs 21% [P = .02]; 15% vs 53% [P < .001], respectively). SARS-CoV-2 was the most frequent pathogen detected in 2020; of 30 infants tested, 20 tested positive. Infants with SARS-CoV-2 were more likely to identify as Hispanic (P = .004), have public insurance or be uninsured (P = .01), exhibited lethargy (P = .02), had feeding difficulties (P = .002), and had lower white blood cell (P = .001), neutrophil (P < .001), and lymphocyte counts (P = .005) than the 81 infants without SARS-CoV-2 infection. None of the infants with SARS-CoV-2 had concurrent serious bacterial infection or detection of another virus. Overall, disease in infants with SARS-CoV-2 was mild. CONCLUSIONS: During the peak of the pandemic, SARS-CoV-2 was the predominant pathogen among febrile infants. Socioeconomic, historical, and laboratory features differed significantly between infants infected or not infected with SARS-CoV-2. None of the 20 infants with SARS-CoV-2 infection had an identified coviral or serious bacterial infection.