The following park species are federally listed as Threatened or Endangered:

Mammals
• Myotis sodalis, Indiana bat - endangered
• Glaucomys sabrinus coloratus, Carolina northern flying squirrel - endangered

Birds
• Picoides borealis, Red-cockaded Woodpecker - endangered

Fish
• Erimonax monachus, Spotfin chub - threatened 
• Etheostoma percnurum, Duskytail darter - endangered
• Noturus baileyi, Smoky madtom - endangered 
• Noturus flavipinnis, Yellowfin madtom - threatened 

Arthropods
• Microhexura montivaga, Spruce-fir moss spider - endangered

Plants
• Geum radiatum, Spreading avens - endangered
• Spiraea virginiana, Virginia spiraea - threatened
• Gymnoderma lineare, Rock gnome lichen - endangered

The following species have been extirpated:
• Canis lupus, Gray wolf - endangered
• Canis rufus, Red wolf - endangered
• Felis concolor couguar, Eastern puma or cougar - endangered

In addition the following Federal Species of Concern are found in the park

Mammals
• Myotis leibii, Eastern small-footed bat
• Sorex palustris, Water shrew
• Sylvilagus obscurus, Appalachian cottontail

Birds
• Ammodramus henslowii, Henslow’s Sparrow
• Contopus cooperi, Olive-sided Flycatcher
• Dendroica cerulean, Cerulean Warbler
• Loxia curvirostra, Red Crossbill
• Poecile atricapillus, Black-capped Chickadee
• Sphyrapicus varius, Yellow-bellied Sapsucker
• Vermivora chrysoptera, Golden-winged Warbler

Amphibians
• Cryptobranchus alleganiensis, Eastern hellbender
• Desmognathus aeneus, Seepage salamander
• Eurycea junaluska, Red-cheeked salamander

Fish
• Percina squamata, Olive darter
• Phoxinus tennesseensis, Tennessee dace

Plants
• Abies fraseri, Fraser fir
• Calamagrostis cainii, Cain’s reed-bent grass
• Cardamine clematitis, Mountain bittercress
• Glyceria nubigena, Smoky Mountain manna grass
• Silene ovata, Blue Ridge catchfly