We report the depredation of a Picoides borealis (Red-cockaded Woodpecker) nest by an Elaphe alleghaniensis (Eastern Rat Snake). Of 38 banded woodpecker groups monitored by video surveillance during 1998–2000, we documented one nest depredation by an Eastern Rat Snake. Woodpecker visitation to the nest area during the depredation event increased substantially compared with pre-depredation nesting behavior. Woodpecker visitation to the nest cavity was minimal during the first six hours after the snake was discovered by the adult woodpeckers. Visitation levels by woodpeckers remained higher than pre-depredation levels while the snake remained in the nest cavity. After the snake's departure from the nest, visitation rates dropped below pre-depredation levels. Woodpeckers continued to visit the cavity during the day and roost in the cavity at night for the remaining seven days of surveillance post-depredation. This same banded woodpecker pair nested in the same cavity in 1999 and fledged 1 female. Overall, we observed a low rate of nest depredation by rat snakes during this study; only one instance was recorded during more than 15,000 hours of video surveillance. Based on the proclivity of Red-cockaded Woodpeckers to re-nest in previous nest cavities, and the potential for snakes to re-climb trees based on past successes, resource managers may want to prioritize placement of snake excluder devices or use of bark-shaving at active cavity trees where snake depredation has occurred, especially if funding is limited. We urge ornithologists to continue to incorporate snake research into their avian research to achieve a greater understanding of predator-prey relationships that impact cavity-nesting birds, especially threatened and endangered species such as Red-cockaded Woodpeckers.