The Mattamuskeet National Wildlife Refuge is a federally protected wildlife refuge located within Hyde County, North Carolina, United States. North Carolina's largest natural lake, Lake Mattamuskeet, is located entirely within the National Wildlife Refuge. The refuge has a total area of .
It is home to the mammalian species white-tailed deer, river otters, red wolves, bobcats, and black bears.
The Lake Mattamuskeet Pump Station, also known as Mattamuskeet Lodge, was listed on the National Register of Historic Places in 1980.
List of largest National Wildlife Refuges