Teenager Noah Caluori and fellow back Benhard Janse van Rensburg are set to make their England debuts after being named on the bench for Saturday's Nations Championship clash with Fiji.
Saracens' 19-year-old rising star Caluori, whose 18 tries made him the joint top try-scorer in the Gallagher Prem this season, comes into Steve Borthwick's matchday squad as Cadan Murley misses out with injury.
The South African-born Janse van Rensburg has this week become eligible to play for England on residency grounds after five years living in the country.
The 29-year-old Bristol back, who does not have English parents or grandparents, made a sole appearance for South Africa's U20 side in 2016, which World Rugby last year no longer tied him to the Springboks at senior level.
Caluori started while Janse van Rensburg featured from the bench in a non-cap fixture against France last month, but their first official senior international appearances will come on Saturday at Everton's Hill Dickinson Stadium, which Fiji are using as their home ground.
The pair are joined on the bench by a third uncapped player, Bristol front row George Kloska, who also started in the unofficial fixture against France.
England lost their Nations Championship opener 45-21 to South Africa in Johannesburg, slumping to a fifth successive Test defeat after ending the Six Nations with four losses earlier this year.
Having been a late call up to the bench for the defeat to South Africa following an injury to George Furbank, Henry Slade comes into the starting XV at outside centre to win his 76th England cap.
The only other change to the starting line-up comes at flanker, where Guy Pepper replaces Tom Curry.
Borthwick has altered the composition of his bench, with second row Charlie Ewels making way to allow a third back on the eight-player bench.
Jamie George continues as captain in the absence of Maro Itoje, with Ollie Chessum and Ellis Genge serving as vice-captains.
"We've had a really positive week of preparation, and the players have worked hard in training," Borthwick said. "We know Fiji will provide a tough challenge. They are a dangerous side who will demand the very best from us.
"It's fantastic to be playing at Hill Dickinson Stadium, which is an outstanding venue. There is a real passion for rugby across the north of England, and we're looking forward to experiencing a brilliant atmosphere in Liverpool."
England complete their trio of summer fixtures with a trip to Argentina next weekend, before the inaugural edition of the competition resumes in November.
England enter the clash with Fiji off the back of a tough 45-21 loss to South Africa which marked a continuation of what has been a poor run of form.
For Fin Smith, while the results have not been great, there are small areas that England can improve in which, he believes, will start to turn around results.
"We watched the game a fair few times and played out quite a few scenarios back on that flight home and ultimately it is no magic potion," Smith told Your Site.
"We just need to do the basic things of the game slightly better, more often. As dull as that is, you play the best team in the world and that is what they teach you.
"It is a tough game and I came off the pitch thinking they were a proper quality outfit.
"I thought credit to South Africa, I thought that was a hell of a performance and they have got some real superstars on that team.
"While saying that, I think there was moments where we had our tails up and we can take a little bit of confidence in that.
"Sometimes it is hard to see the light when we have had some tough results and some not so good performances.
"But it is just the small things done on repeat in test matches and if we start winning a few more of those small moments, then scoreboards will turn and teams will then start feeling under pressure."
England team to face Fiji:
Starting XV: 15 Marcus Smith, 14 Tommy Freeman, 13 Henry Slade, 12 Seb Atkinson, 11 Immanuel Feyi-Waboso, 10 Fin Smith, 9 Jack van Poortvliet; 1 Ellis Genge, 2 Jamie George (c), 3 Joe Heyes, 4 Alex Coles, 5 George Martin, 6 Ollie Chessum, 7 Guy Pepper, 8 Ben Earl.
Replacements: 16 Luke Cowan-Dickie, 17 Asher Opoku-Fordjour, 18 George Kloska, 19 Tom Curry, 20 Henry Pollock, 21 Alex Mitchell, 22 Benhard Janse van Rensburg, 23 Noah Caluori.
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