Peak populations of waterfowl in the fall and winter can exceed 10,000 birds, with the majority being mallards. Other ducks seen include wigeon, green-winged teal, blue-winged teal, pintail, and gadwall. For many reasons, the large migrating flocks of Canada geese are gone, but the refuge is still used by several hundred migrating Canadas and a growing flock of resident geese.

The refuge is also an important stopping point for bald eagles, snipe, woodcock, hawks, owls, herons, and egrets. In addition, the bottoms of Brown Creek provide excellent habitat for many migratory songbirds, including blue grosbeak, scarlet tanager, and prothonotary warbler. The endangered red-cockaded woodpecker no longer uses the refuge, but areas of potential habitat still remain. Bobwhite quail and wild turkey are popular upland game birds. The refuge bird list includes 188 species.

The refuge mammal list contains 28 species, including white-tailed deer, red and gray fox, bobcat, beaver, gray squirrel, and fox squirrel. Amphibian and reptile species number 28 and 48, respectively. These include spotted salamander, American toad, pickerel frog, river cooter, box turtle, rough green snake, and copperhead. Refuge waters provide an excellent fishery, which includes channel catfish, largemouth bass, and several sunfish species.