Ashepoo River is a short blackwater river in South Carolina, United States. It rises in a confluence of swamps south of Walterboro, flows in a southeast direction and empties into Saint Helena Sound at . The entire course of the river lies within the boundaries of Colleton County.
The Ashepoo basin forms part of the ACE Basin, a coastal conservation area that encompasses its bottomlands confluence with the Combahee and Edisto river basins. (The refuge's name is formed from the first letters of the names of the three rivers: A-C-E). Many people enjoy fishing and boating on the Ashepoo River and others in South Carolina.
The name comes from the Ashepoo subtribe of the Cusabo Indians.
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