Tom Wood and Jonny May are among those to have been recalled to England's Test squad, while six uncapped players have also been selected amid an injury crisis.
The influential Maro Itoje became the latest England star to be ruled out of matches against South Africa, Fiji, Argentina and Australia on Monday, due to a fractured hand.
Head coach Eddie Jones was already without a host of players through injury, including George Kruis, Anthony Watson, Jack Nowell, James Haskell, Sam Jones and Jack Clifford.
With so many players unavailable, Northampton Saints flanker Wood has been given an opportunity to impress.
Wood has yet to feature under Jones and revealed earlier this year that the Australian had labelled his performances "distinctly average" when explaining his initial omission.
Wing May and Gloucester team-mate Ben Morgan have also been named in a 33-man squad, together with Bath second-row Dave Attwood.
In addition, Jones has called up half a dozen uncapped players: Harlequins prop Kyle Sinckler, another Bath second-row in Charlie Ewels, Wasps flanker Nathan Hughes, Saracens fly-half Alex Lozowski, Worcester Warriors centre Ben Te'o and Sale Sharks wing Mike Haley.
"With a number of influential players missing through injury we have two weeks to prepare a robust and resilient team to meet the challenges set for us," said Jones.
"Our training camp in Portugal is a great opportunity to spend a week together, focus on putting our game plans in place and for new players to understand the England way.
"I'm confident we can prepare well and put together a matchday 23 which is full of pride, energy and commitment to give South Africa the game of their lives."
England squad to face South Africa, Fiji, Argentina and Australia:
Forwards: Dave Attwood, Dan Cole, Charlie Ewels, Ellis Genge, Jamie George, Teimana Harrison, Dylan Hartley, Nathan Hughes, Joe Launchbury, Courtney Lawes, Joe Marler, Ben Morgan, Chris Robshaw, Kyle Sinckler, Tommy Taylor, Billy Vunipola, Mako Vunipola, Tom Wood.
Backs: Mike Brown, Danny Care, Elliot Daly, Owen Farrell, George Ford, Alex Goode, Mike Haley, Jonathan Joseph, Alex Lozowski, Jonny May, Semesa Rokoduguni, Henry Slade, Ben Te'o, Marland Yarde, Ben Youngs.