Cypress Creek National Wildlife Refuge is located in southernmost Illinois, within the Cache River Watershed. The refuge was established in 1990 under the Emergency Wetlands Resource Act of 1986 to protect, restore, and manage wetlands and bottomland forests that provide habitat for waterfowl and other migratory birds, resident wildlife, and endangered and threatened species. Currently, the refuge protects 15,000 acres, with the vision of a 35,000-acre contiguous tract of land connected by remnants of cypress-tupelo swamps, oak barrens, and vast stands of bottomland forests. The refuge and surrounding Cache River Wetlands are considered Illinois' Bayou - a large swamp/wetland complex in the Midwest which harbors a rich collection of biologically significant natural communities. The Cache River and Cypress Creek Wetland was designated a "Wetland of International Importance" (Ramsar site) for its rich diversity of plant and animal communities; it claims some of the oldest living trees east of the Mississippi River and harbors 91% of Illinois' high-quality swamp habitat. The refuge is a member of a unique partnership to restore and manage the Cache River Wetlands. Together, the refuge, the Illinois Department of Natural Resources (IDNR), The Nature Conservancy, and Ducks Unlimited share a common goal to protect and restore 60,000 acres along a 50-mile corridor of the Cache River. Wildlife observation, hiking, canoe trails, and hunting and fishing are just a few of the activities offered at this new refuge.

Cypress Creek National Wildlife Refuge is located in the southernmost portion of Illinois, with lands located in Union, Pulaski, Alexander, and Johnson counties. Take Interstate 57, and exit at #18, Shawnee College Road. Travel approximately 7.1 miles east to the refuge office located on the Shawnee College Rustic Campus, Building D. The refuge is approximately 22 miles north of Cairo, Illinois, and 35 miles south of Carbondale, Illinois.