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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 32°29′24″N 80°25′26″W / 32.49°N 80.42389°W. The entire course of the river lies within the boundaries of Colleton County. The name comes from the Ashepoo subtribe of the Cusabo Indians. Caeser P. Chisolm received a charter to operate ferry service across the Ashepoo River.