Flanker Tom Johnson, number eight Tom Waldrom and wing Charlie Sharples have all been dropped from England's 23-man squad to face South Africa.
The trio started in England's 20-14 defeat to Australia at Twickenham last weekend.
Harlequins loosehead Joe Marler has been ruled out with a knee ligament injury, opening the way for London Irish star Alex Corbisiero to return after overcoming a knee injury of his own.
Wasps' James Haskell and Gloucester number eight Ben Morgan have both been included in the squad, replacing Waldrom and Johnson.
London Irish centre Jonathan Joseph has taken Sharples' place in the matchday squad after recovering from an ankle injury.
"We have made some changes this week to freshen up the squad before the challenge of South Africa," said England head coach Stuart Lancaster, who will confirm his starting XV on Thursday.
"Unfortunately that means one or two players miss out who were in the matchday squad against Australia.
"But they have all added value with their contributions in training and the games and I am sure they will be looking to play well for their clubs and force their way back in.
"The changes however give opportunities to those who have been pushing hard and we feel will add energy and balance to the team ahead of the significant South African challenge."
Mouritz Botha has been added to the squad as provisional injury cover for Geoff Parling, who is nursing a knee problem but the England medics expect him to be fit.
England's 23-man squad:
Backs (10): Chris Ashton (Saracens), Brad Barritt (Saracens), Mike Brown (Harlequins), Danny Care (Harlequins), Owen Farrell (Saracens), Toby Flood (Leicester), Alex Goode (Saracens), Jonathan Joseph (London Irish), Manu Tuilagi (Leicester), Ben Youngs (Leicester)
Forwards (14): Mouritz Botha (Saracens), Alex Corbisiero (London Irish), Dan Cole (Leicester), James Haskell (Wasps), Joe Launchbury (Wasps), Ben Morgan (Gloucester), David Paice (London Irish), Tom Palmer (Wasps), Geoff Parling (Leicester), Chris Robshaw (Harlequins, capt), Mako Vunipola (Saracens), David Wilson (Bath), Tom Wood (Northampton), Tom Youngs (Leicester)