During the winter in 2008, Iowa experienced an increase in sudden unexplained infant deaths (SUIDs). SUIDs and infectious causes of infant deaths generally average 3 monthly (SD = 1.0) in Iowa. However, in January 2008, 9 infant deaths were reported to the Iowa Department of Public Health and the Iowa Office of the State Medical Examiner. Between January and March of 2008, joint investigation of 22 SUIDs was conducted. The investigations required the involvement of multiple medical examiners from various jurisdictions, testing for pathogens at the University Hygienic Laboratory, epidemiologic support from the Iowa Department of Public Health, and consultation with the Centers for Disease Control and Prevention. The preliminary hypotheses for the increase in the infant mortality included viral respiratory disease and/or possible novel respiratory viral infections being the cause. Collaboration between public health and the medical examiner offices resulted in timely assessment of the cases. While no single causative agent was responsible for the increase seen in the number of infant deaths, respiratory pathogens played a role in the deaths of 15 of 22 children.