A marked decline in the Picoides borealis (Red-cockaded Woodpecker [RCW]) population at Noxubee National Wildlife Refuge, MS, was observed in 2002. Demographic changes—including absence of hatch-year birds, decreases in size of known groups, and loss of known groups—were identified during annual fall surveys and are uncharacteristic of RCW populations. In 2003, a serosurvey of 28 adult RCWs was conducted to investigate the presence of West Nile virus (WNV) exposure in the population, possibly providing insight into whether WNV may have been responsible for this decline. Blood smears were also examined from these birds for blood parasites. We found no evidence of West Nile virus exposure or blood parasites in any of the RCWs sampled. Further monitoring of the RCW population and WNV activity in other species at Noxubee NWR is recommended to further evaluate the potential role of WNV and blood parasites in their decline.