Northern riffleshell and clubshell mussels are small to medium sized mussels. These two species are critically imperiled, having lost more than 95 percent of their historic range. However, the surviving northern riffleshell in Pennsylvania are some of the best remaining in the world. French Creek is home to these and 26 other mussel species.

Although you may rarely see them, mussels are an integral part of a healthy stream ecosystem. They obtain food by filtering out suspended particles from the water leaving streams and rivers clearer. Mussels also serve as food for some species of birds, mammals, reptiles, and fish. 

Bald eagles nest on the refuge. There are currently three eagle nests on the refuge. Eagles are most active during nesting season. Lucky visitors may even catch their elaborate mating flight. Nesting generally occurs in late February with chicks hatching in April.

Red-tailed hawks and American kestrels are common raptors that nest here as well. Both may be seen over open fields hunting for small mammals or birds.
 

Wood duck, hooded merganser, mallard, blue-winged teal and Canada goose regularly nest on the refuge; another eight waterfowl species use the refuge during migration. Peak duck and goose populations appeared to typically be higher during fall and spring migrations than during breeding, with spring migratory populations usually being higher than fall migratory populations. Cavity nesters like the wood duck and hooded mergansers are around during the breeding season, but might be difficult to see since they like to stay hidden.
 

The refuge is entirely within the French Creek watershed. This watershed is considered an ecologically significant watershed nationally, as well as in Pennsylvania, contains globally rare freshwater mussels and fish. The restoration and maintenance of the riparian-riverine ecosystem has the highest priority for management. The Seneca Division, given the documented presence of endangered freshwater mussels, associated host fish species, rare plant communities, and high water quality, is the highest priority for specific management strategies. Other animals found here are spotted turtle, wood turtle, hellbender, and river otter.

Refuge wetlands provide habitat for waterfowl, marsh and waterbirds, bald eagles and many other wetland species. Over 5,700 acres of wetland, including beaver floodings, marshes, swamps, man-made impoundments, and creeks provide a diversified wetland habitat type.

Currently the refuge manages more than 3,487 acres of upland forests. Associated tree species include red maple, striped maple, mountain maple, white ash, white pine, black cherry, and American basswood In addition, river valleys in the region historically contained riparian deciduous forests, characterized by flood-tolerant trees such as silver maple, sycamore, black willow, river birch, pin oak, ashes, box elder and hemlock These mature forests support breeding habitat for some forest interior birds of concern like cerulean warbler, black-billed cuckoo, and scarlet tanager.