Winger Charlie Sharples, flanker Tom Johnson and No8 Thomas Waldrom have all been axed from the 23-man squad as England look to respond to their frustrating 20-14 loss to Australia last weekend.
Loosehead prop Joe Marler misses out with a knee ligament injury, with Alex Corbisiero expected to return in his place.
Back-row forwards Ben Morgan and James Haskell have both been included in the squad for the first time this autumn, replacing Johnson and Waldrom.
Sharples has been supplanted by London Irish centre Jonathan Joseph, who has shaken off an ankle injury to return to the squad.
Lancaster will confirm his starting line-up tomorrow and will be hoping they can improve England’s recent record against South Africa.
They have not won against the Springboks since 2006, losing 22-17 and 36-27 in South Africa during the summer before regrouping to draw 14-14 in June.
Fly-half Owen Farrell, meanwhile, believes his rivalry with Toby Flood for the No 10 jersey can benefit the side. Farrell has made an impressive start to his international career, debuting against Scotland in February, and scoring 83 points in 10 Tests. However the 21-year-old has been overlooked for the last four Tests, filling different roles off the bench, with Leicester’s Flood getting the nod at fly-half.
“It is a competitive environment, with lots of good players pushing to be involved. What we have, though, is a group of players who are putting the team first rather than any individual goals. Everyone encourages each other,” said Farrell.
“I think there is a healthy competition between Toby and myself. We are constantly talking on how to break teams down and how to better the team. He is a world-class player and it is great to be able to learn off him. We push each other.”
Despite losing to Australia on Saturday, Farrell insists the squad should remain upbeat.
“There were lots of positives to come out of the Australia game, but we know that there is stuff we need to work on too,” he added.
“We know it will be a massively physical game against South Africa and that is what our focus is now on. We had those three games against them in the summer and I felt we got better as the series went on. It is just those fine margins when two good teams go head to head.”