Common Kingsnakes (formerly known collectively as Lampropeltis getula) are experiencing localized declines throughout the southeastern United States. Because there have been limited studies to determine how snakes regulate prey populations, and because Kingsnake declines may result in ecosystem impacts, we evaluated the hypothesis that Kingsnakes regulate the abundance of one of their prey, the venomous Copperhead (Agkistrodon contortrix). We generated a database of captures of the two species across the southeastern United States and, while controlling for large-scale habitat preferences, identified a negative relationship between the relative abundance of Kingsnakes and the relative abundance of Copperheads. Our results are correlative but consistent with the hypothesis that Copperhead populations experience a release from predation pressure where Kingsnake abundances are low. We suggest that Kingsnake declines, which are occurring for unknown reasons, are having ecological effects in affected ecosystems. We further highlight the potential role that snakes play in influencing the population dynamics of their prey.