We performed a 7-year registry-based retrospective study. We included 1365 infants younger than 3 months of age with fever without a source; 81 (5.9%) had <5000 leukocytes/mm(3). Among the 1021 well-appearing 29- to 90-day-old infants, prevalence of serious bacterial infection (SBI) was 13.8% for those with a normal white blood cell count, 6.8% for those with leukopenia (odds ratio, 0.45), and 36.6% for those with leukocytosis (odds ratio, 3.59). None of the 9 well-appearing febrile neonates with leukopenia developed an SBI. Leukopenia, in well-appearing young febrile infants, should not be considered as an SBI risk factor.