Objective: Our objective was to describe clinically significant infections in a cohort of afebrile neonates who underwent an emergency department (ED) septic workup because of the history of a measured fever at home. Methods: Retrospective medical record review of all infants 3/4 28 days of age who presented to our tertiary care pediatric ED between Jan. 1, 1999, and Aug. 22, 2002, underwent lumbar puncture in the ED, had a reported temperature at home of > = 38°C, and an ED triage temperature of < 38°C. Laboratory and radiographic results were tabulated. Results: During the study period, 206 neonates underwent lumbar puncture in our ED. Of these, 108 were excluded because their home temperature was not documented, and 71 were excluded because they were still febrile on presentation to the ED. The study group consisted of the remaining 27 subjects, 4 of whom had received acetaminophen prior to ED arrival. Infections were confirmed in 10 (37%) subjects (3 urinary tract infections, 2 aseptic meningitis, 1 enterovirus meningitis, 1 respiratory syncytial virus bronchiolitis, 1 rotavirus enteritis and 2 pneumonias). Conclusions: Clinically important infections are not uncommon among afebrile neonates undergoing ED septic workup because of a measured fever at home. Some diagnostic testing is warranted in this group, although the clinical utility and indications for specific test modalities remain unclear.