Henry Slade is out of the tour of Argentina and the United States with a hand injury, leaving England with inexperienced midfield options as they attempt to seal a series win over the Pumas.
Slade played the full 80 minutes in the 35-12 first-Test win over Argentina in La Plata on Saturday but will miss the rematch in San Juan this weekend.
Seb Atkinson made his first Test appearance in La Plata while Max Ojomoh, Luke Northmore and Oscar Beard – the other specialist centres in the 36-player squad – are still uncapped.
Fraser Dingwall and Ollie Lawrence, who emerged as England’s first-choice midfield during the Six Nations, are both injured while the versatile Elliot Daly has returned from the British and Irish Lions tour of Australia with a fractured arm.
Slade, who won his 73rd England cap against Argentina, was also a back-up option at fly-half, with uncapped Charlie Atkinson the only direct cover for the experienced George Ford.
Co-captains Ford and Jamie George and flanker Sam Underhill – with 102, 100 and 41 caps respectively – are now the only players with more than 40 caps in the squad.
England, whose tour will conclude with a one-off Test against the United States on 19 July, have no plans to summon a replacement for Slade.
Steve Borthwick’s side produced one of their best performances of the head coach’s reign in La Plata, surviving the sin-binning of Alex Coles and Seb Atkinson to lead 3-0 at half-time, before accelerating away to victory via four second-half tries.
The win takes England above their opponents to fifth in the world ranking.
The Pumas, who rested some of their France-based players for the first Test, have brought in Bordeaux-Begles second row Guido Petti for the second game.
The 30-year-old, who scored a try in their Top 14 final loss against Toulouse on 28 June, will join up with Harlequins next season.