England's players are only allowed to start in three of the four November Tests. Saturday's match at Twickenham and a second game on Nov. 25 against the Springboks completes its international program.
Mark Cueto has recovered from an ankle injury and replaces right-winger Paul Sackey, and Josh Lewsey takes over from Ben Cohen on the other wing.
Centre Mathew Tait, scrum half Peter Richards, prop Andrew Sheridan, lock Tom Palmer and flanker Joe Worsley come in for Anthony Allen, Shaun Perry, Perry Freshwater, Danny Grewcock and Lewis Moody, respectively.
Captain Martin Corry has been moved from blindside flanker to No. 8, while Charlie Hodgson stays at fly half after being taken off for tactical reasons during the 25-18 defeat to Argentina on Saturday.
In two other positional switches, Jamie Noon moves from outside to inside center and Pat Sanderson has swapped with Corry.
Prop Phil Vickery returns to the squad for the first time since November 2005. He was named on the bench.