Shorebird use of horseshoe crab (Limulus polyphemus) eggs as food items has been well documented along the Atlantic coast of the United States at northeastern stopover sites such as the Delaware Bay. However, the relationship between migratory shorebirds and horseshoe crab eggs has not been well studied in the South Atlantic Bight. The objective of our study was to assess the spatial and temporal overlap between the density of horseshoe crab eggs and the relative abundance of foraging shorebirds during spring migration in the Cape Romain-Santee Delta Region (CRSD), South Carolina, USA. The CRSD is a site of international importance for shorebirds that supports ∼100,000 shorebirds annually. We also sought to determine if horseshoe crab eggs were present in the diets of shorebirds at these sites. We monitored study plots between March and June 2015–2016 at predicted horseshoe crab spawning sites on beaches throughout Cape Romain National Wildlife Refuge. We conducted weekly shorebird surveys and collected core samples of beach substrate twice per month to measure densities of horseshoe crab eggs. We found a positive correlation between number of foraging shorebirds and horseshoe crab eggs for both years. In a molecular analysis of shorebird fecal samples, 95% of the samples tested contained DNA from horseshoe crab eggs. The spatial and temporal overlap between shorebirds and horseshoe crab eggs, and the dietary analysis of fecal samples, suggest that there are areas of localized horseshoe crab spawning that shorebirds can utilize as a food source during spring in Cape Romain National Wildlife Refuge.