Carbon monoxide (CO) poisoning is a leading cause of unintentional poisoning deaths in the United States. CO is an odorless, colorless gas that usually remains undetectable until exposure results in injury or death. CO poisoning is preventable; nonetheless, unintentional, non--fire-related CO poisoning is responsible for approximately 15,000 emergency department visits and nearly 500 deaths annually in the United States. National estimates of CO exposures have been based on secondary data sources, such as hospital administrative records, and are limited to exposures treated within the health-care system. To describe more completely the national burden of CO exposure and risk factors associated with vulnerable populations, CDC used data from the National Poison Data System (NPDS) to characterize reported unintentional, non--fire-related CO exposures, including those that were managed at the site of exposure and were not treated at a health-care facility. Among 68,316 CO exposures reported to poison centers during 2000--2009, a total of 30,798 (45.1%) were managed at the site of exposure with instructions from the poison center by telephone, 36,691 (53.7%) were treated at a health-care facility, and the management site for the remainder was unknown. Although symptoms varied slightly between persons managed on-site and those treated at a health-care facility, most CO exposures occurred at home and most often involved females, children aged ≤17 years, and adults aged 18--44 years. Surveillance and analysis of data from NPDS and secondary sources might provide a more comprehensive description of the burden of CO exposure in the United States and assist in the development of interventions better targeted to high-risk populations.