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The Sixes River is a river, approximately 30 mi (48 km) long, in southwestern Oregon in the United States. It drains a rugged region of the Coastal Range along the Pacific coast south of Coos Bay.
It rises in the mountains of northern Curry County, south of Sugarloaf Mountain in the Siskiyou National Forest. It flows generally west, through Grassy Knob Wilderness, the town of Sixes, and eventually enters the Pacific just north of Cape Blanco. The mouth of the river is along the coast in Cape Blanco State Park.
On March 30, 2009, 13,700 acres (55.4 km2) along the North and South Forks of Elk River and the upper Middle Fork of Sixes River were designated as the Copper Salmon Wilderness. The area contains one of the nation's largest remaining stands of low-elevation old-growth forest and one of the healthiest salmon, steelhead, and cutthroat trout runs in the continental United States along the north Fork of the Elk River, as well as stands of vulnerable Port Orford cedar and endangered marbled murrelets and northern spotted owls.