The 3,750-acre Clarence Cannon National Wildlife Refuge is located in the floodplain of the Mississippi River, adjacent to Pool No. 25. The refuge's diversity of habitats supports waterfowl, wading birds, shorebirds, and songbirds. Although it is protected by a levee, the refuge provides flood storage in periods of high water.

Clarence Cannon Refuge is managed by Great River National Wildlife Refuge, which is part of the Mark Twain National Wildlife Refuge Complex.