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The Cypress Creek National Wildlife Refuge is an American wildlife refuge. It is located in the Cache River watershed in southernmost Illinois, largely in Pulaski County, but with extensions into Union, Alexander, and Johnson counties. The refuge was established in 1990 under the authority of the Emergency Wetlands Resources Act of 1986. The refuge protects over 16,000 acres (65 km2) of the Cache River wetlands, and has a purchase boundary (ultimate goal for area protection) of 36,000 acres (146 km) contiguous.