The Virginia opossum (Didelphis virginiana) is the only marsupial in North America with a natural range north of Mexico. Its range is widespread throughout the United States, including Illinois. Virginia opossums are opportunistic omnivores that will eat a variety of fruits, grains, insects, and even carrion. They are a ground-foraging species, with frequent soil contact allowing for potential exposure to heavy metal contaminants in terrestrial environments. They are also opportunists that thrive in human-altered ecosystems, including peri-urban environments. Lead is a naturally occurring element and highly toxic metal that is abundant in the soil, primarily due to anthropogenic factors such as fossil fuel use, paint, industrial production waste, and battery recycling. Furthermore, carrion and offal piles containing lead bullet fragments remaining from hunting result in environmental contamination of this heavy metal. Few studies exist on lead exposure in the Virginia opossum. This pilot study evaluates the blood lead burden of 16 free-ranging Virginia opossums presented to a wildlife rehabilitation facility, compared with 16 wild-caught Virginia opossums trapped in grassland, maintained forest, or mixed ecotones. In other species, lead toxicosis has been associated with cognitive dysfunction that may increase the likelihood of trauma or injury in a free-ranging setting. In addition, a high incidence of Virginia opossums presenting for wildlife rehabilitation do so as result of human–animal conflict. Therefore, it was anticipated that individuals presenting for wildlife rehabilitation would have significantly higher blood lead concentrations than their free-roaming counterparts. In this study, every Virginia opossum had measurable blood lead concentrations and the average blood lead concentration of the rehabilitated group was 2.7 times higher than that measured in wild-caught Virginia opossums. These results suggest that Virginia opossums are exposed and susceptible to lead toxicosis due to their diet and foraging behaviors, making them more prone to subsequent injury and presentation to wildlife rehabilitation centers.