South Carolina Highway 781 (SC 781) is a 3.561-mile (5.731 km) primary state highway in the U.S. state of South Carolina.

It is used as part of a bypass south of Aiken, between Augusta and Williston, in conjunction with U.S. Route 278 (US 278).

SC 781 is a two-lane rural connector highway between US 278 and US 78.

[2] Established in 1940 as a new primary route, it traversed from SC 28 in Beech Island east to US 78 west of Williston.

[3][4] The entire highway is in Aiken County.