Anthony Watson has been ruled out of England's Six Nations opener against France in Paris with a calf injury.
Watson's injury clears the way for either Ollie Thorley or George Furbank, both 23, to make their Test debut in the back three.
Prop Will Stuart, also 23, has also been retained in a 25-man squad and is set to win a first cap from the bench.
Hooker Luke Cowan-Dickie will re-join the squad after leaving camp earlier in the week.
With Watson unavailable for selection, head coach Eddie Jones is unable to revert to his preferred World Cup combination in the backline.
It leaves Jones with two options in the back three: either Elliot Daly will continue at full-back with Jonny May and the uncapped Thorley on the wings, or Daly will move to the wing with Furbank coming in for his first taste of international rugby.
Centre Ollie Devoto has also been retained, but Jones is likely to select the World Cup axis of George Ford, Owen Farrell and Manu Tuilagi in the midfield.
With Thorley, Furbank and Stuart all in the frame to make their debuts, Tuilagi has welcomed the input of the new faces in camp.
"I feel very old, asking those boys how old they are. I remember [being a young player] back in the day," Tuilagi told BBC 5 Live.
"But they are good boys and quality players and they are willing to learn. As a young lad, that's important."
Saracens' in-form back-row forward Ben Earl is one of the players released back to his club, meaning Tom Curry is likely to play number eight in Billy Vunipola's absence with the versatile Lewis Ludlam on the bench.
Courtney Lawes is set to move from the second row to the blind-side flank to pack down alongside Curry and Sam Underhill in the back row.
England travel from their warm-weather training camp in Portugal to Paris on Thursday before naming their starting XV and replacements on Friday morning at 10:30 GMT.
England's 25-man squad:
Forwards: Cowan-Dickie, T Curry, Ewels, Genge, George, Itoje, Kruis, Lawes, Ludlam, Marler, Sinckler, Stuart, Underhill, M Vunipola.
Backs: Daly, Devoto, Farrell, Ford, Furbank, Heinz, Joseph, May, Thorley, Tuilagi, Youngs.