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The Salkehatchie River originates near the City of Barnwell, South Carolina and accepts drainage from Turkey Creek and Whippy Swamp before merging with the Little Salkehatchie River to form the Combahee River Basin, which empties into Saint Helena Sound and the Atlantic Ocean. Prior to the confluence, the Little Salkehatchie River accepts drainage from Lemon Creek, Buckhead Creek, and Willow Swamp.