England Women will be without injured trio Lauren James, Ella Toone and Lauren Hemp when they face Emma Hayes' USA side at Wembley on November 30.
Manchester City announced that Hemp had undergone knee surgery on Tuesday, while Toone and James are both suffering with calf issues.
Chelsea's Niamh Charles and Aston Villa defender Lucy Parker are also sidelined.
Sarina Wiegman has therefore handed Manchester City's Laura Blindkilde Brown and Leicester City's Ruby Mace, both 21, their first senior international call-ups.
Meanwhile, Manchester United defender Gabby George, who suffered an ACL injury last year, has returned to the fold for the first time since November 2022.
The 24-player squad will meet at St George's Park next week before hosting the USA at Wembley later this month and Euro 2025 hosts Switzerland on December 3 at Bramall Lane.
Wiegman was asked about injuries to Hemp and Toone after announcing her squad but was unable to offer an update on their expected time frames for a return.
"[Hemp] Not from me. She had surgery and I think she will be okay. It will take a while to get back but I am not worried."
On Toone, she added: "She is out for a period and that became clear pretty quickly that she wouldn't be able to be part of this squad."
Wiegman was quick to add that the injuries to key players will provide players like Blindkilde Brown and Mace with an opportunity to impress, as the England boss called on them to "compete" for a place immediately.
"Young players and very talented players," Wiegman said after handing the duo their first call-ups. "They have done very well in the U23s and it's an opportunity to see them in this environment. I hope they start competing straight away.
"It is part of football. You want the best players in your squad but sometimes they are injured. Other players then have the opportunity to step up. We will see them back."
Chloe Kelly has kept her spot in the squad, despite only starting one game for Manchester City in the WSL this season, but the England boss hinted that this might not have been the case if the previously noted players had not suffered injuries.
"I think it is a concern," Wiegman said when asked if Kelly's game time at City was a concern. "That is her situation, competition at Manchester City is high.
"We have some injuries up front, like Lauren Hemp and Lauren James. Chloe knows she is not in the best position but she has enough credit to bring her in, related to the whole team and availability."
Goalkeepers: Mary Earps (PSG), Hannah Hampton (Chelsea), Anna Moorhouse (Orlando Pride).
Defenders: Lucy Bronze (Chelsea), Millie Bright (Chelsea), Jess Carter (Gotham), Alex Greenwood (Manchester City), Leah Williamson (Arsenal), Esme Morgan (Washington Spirit), Millie Turner (Manchester United), Gabby George (Manchester United), Maya Le Tissier (Manchester United).
Midfielders: Grace Clinton (Manchester United), Fran Kirby (Brighton), Jess Park (Manchester City), Laura Blindkilde Brown (Manchester City), Georgia Stanway (Bayern Munich), Keira Walsh (Barcelona), Ruby Mace (Leicester).
Forwards: Aggie Beever-Jones (Chelsea), Chloe Kelly (Manchester City), Beth Mead (Arsenal), Alessia Russo (Arsenal), Jess Naz (Tottenham).
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