Endangered and Threatened Species on the Refuge: southern bald eagle, Arctic peregrine falcon, brown pelican , wood stork, West Indian manatee, Florida black bear, American alligator, eastern indigo snake, gopher tortoise, green sea turtle, Kemp's Ridley sea turtle, loggerhead sea turtle.

Other Wildlife Species: Small numbers of waterfowl winter on the refuge each year, and include: red-breasted merganser, American widgeon, blue and green-winged teal, northern pintail, wood duck, lesser scaup, and ring-necked duck.

• Marsh and water birds include: double crested cormorant, anhinga, great blue heron, little blue heron, tri-colored heron and green backed heron, snowy and great egret, black-crowned night heron, yellow-crowned night heron, white ibis and common moorhen.
• Shorebirds include killdeer, black-bellied plover, lesser yellowlegs, spotted sandpiper, common snipe, least sandpiper, and dunlin. Laughing gulls and royal terns are also seen on the refuge.
• The most commonly seen raptors include red-tailed and red-shouldered hawks, and ospreys.
• A variety of neotropical migrants may be found on the upland, wooded portions of the refuge.
• Game mammals include white-tailed deer, feral hog, and black bear.
• Raccoons and otters are commonly found in the salt marsh areas.
• Bobcats and coyotes are occasionally seen.
• Atlantic bottle-nosed dolphins are often seen in the Chassahowitzka River.
• The refuge supports a healthy population of Florida cottonmouth, eastern diamondback rattlesnake, diamondback terrapin, and Florida box turtle.
• Since the refuge contains approximately 10,000 acres of estuarine habitat varying from fresh to saltwater, a wide variety of fish species are plentiful. Scallops and blue crabs may also be found and are commercially important.