Manchester United boss Erik ten Hag is expected to name the likes of David de Gea, Victor Lindelof, Scott McTominay and Anthony Martial in his starting side for Wednesday's mid-season friendly with Cadiz.
The 20-time English champions have travelled to Spain for a week-long training camp, which will also include a game against Real Betis, as the team prepare for the return of competitive action.
Lisandro Martinez, Casemiro, Antony, Fred, Christian Eriksen, Harry Maguire, Luke Shaw, Marcus Rashford, Raphael Varane, Tyrell Malacia, Bruno Fernandes, Diogo Dalot and Facundo Pellistri will all be missing for Man United due to their involvement in the 2022 World Cup.
Cristiano Ronaldo is also with Portugal at the competition, but the 37-year-old has now had his contract terminated by the club.
Kobbie Mainoo, Charlie Savage, Zidane Iqbal and Charlie McNeill are among the youngsters who will be hoping to be given opportunities to impress during the two matches.
Meanwhile, fit-again Aaron Wan-Bissaka and Brandon Williams could also be potentially handed starts, having overcome their fitness problems.
Donny van de Beek failed to make the Netherlands squad for the World Cup and could also start, while Anthony Elanga and Alejandro Garnacho are also likely to be in the side.
Axel Tuanzebe has not made the trip due to injury, though, and there is also no Jadon Sancho, who is currently undergoing a personalised training programme.
Manchester United possible starting lineup: De Gea; Wan-Bissaka, Lindelof, Mengi, Williams; McTominay, Iqbal, Van de Beek; Elanga, Martial, Garnacho
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