The Caloosahatchee National Wildlife Refuge is a 40-acre property within the city limits of North Fort Myers. The wildlife refuge was officially designated on July 1, 1920 and is administered as part of the J.N. "Ding" Darling National Wildlife Refuge Complex. The property is located on the Caloosahatchee River and is closed to the public.

Since the refuge was first designated, dredging of the river, new shoreline development and construction of the nearby Interstate 75 bridge has changed the appearance and physical arrangement of the original upland island habitats and mangrove swamp shorelines. Today, the refuge is located in the outflow of Florida Power & Light's Orange River Power Plant. The warm water from that outflow has made Caloosahatchee into a major wintering area for the endangered West Indian manatee.

Adjacent to the refuge is the Lee County Manatee Park, which offers a manatee viewing area. Access to the area is by boat only but the numerous oyster bars and the fragile seagrass beds in the area are easily damaged. Because the area is often frequented by manatees, boat speed restrictions are strictly enforced. You'll also often find eastern indigo snakes, bald eagles and wood storks in addition to a wide variety of shorebirds, waterfowl, wading birds, raptors and neotropical migratory birds in the area. No hunting is allowed and environmental education opportunities are extremely limited.