BACKGROUND: Molecular diagnostic methods enhance the sensitivity and broaden the spectrum of detectable respiratory viruses in febrile infants </=90 days of life. We describe the occurrence of respiratory viruses in this population, as well as the rates of serious bacterial infection (SBI) and respiratory viral coinfection with regard to viral characteristics. METHODS: This was a prospective observational cohort study performed in the emergency department that included previously healthy febrile infants </=90 days of life. Clinical and historical characteristics were documented, and a respiratory nasal wash specimen was obtained from each patient. This sample was tested for 17 common respiratory pathogens, and a chart review was conducted to ascertain whether the infant was diagnosed with an SBI. RESULTS: In a 12-month period, 67% of the 104 recruited febrile infants were positive for a respiratory virus. The most commonly detected viruses were rhinovirus, respiratory syncytial virus, enterovirus and influenza. The rate of respiratory viral and SBI coinfection was 9% overall, and infants with either a systemic respiratory virus or negative viral testing were 3 times more likely to have an SBI than those with viruses typically restricted to the respiratory mucosa (95% confidence interval: 1.1, 9.7). CONCLUSIONS: Respiratory viruses are readily detectable via nasopharyngeal wash in febrile infants </=90 days of life. With the enhanced sensitivity of molecular respiratory diagnostics, rates of coinfection of respiratory viruses and SBI may be higher than previously thought. Further investigation utilizing molecular diagnostics is needed to guide usage in febrile infants </=90 days.