Manchester United will be unable to call upon Noussair Mazraoui, Amad Diallo and Bryan Mbeumo while the trio are involved in the Africa Cup of Nations.
Mazraoui (Morocco) was prevented from featuring against Bournemouth in the Premier League last time out, but Amad (Ivory Coast) and Mbeumo (Cameroon) were both involved before linking up with their countries for the tournament.
The competition starts on December 21 and ends on January 18, so depending on how Morocco, Ivory Coast and Cameroon perform, the trio could miss as many as seven matches.
Man United will face Aston Villa, Newcastle United, Wolverhampton Wanderers, Leeds United, Burnley and Manchester City in the Premier League during AFCON, while they will take on Brighton & Hove Albion in the third round of the FA Cup on January 11.
Here, Sports Mole looks at how Ruben Amorim's side could line up without their AFCON stars.
© Imago / Pro Sports Images
Maguire, De Ligt would improve Man United's shaky defence
Matthijs de Ligt and Harry Maguire are both still sidelined, with the duo again ruled out of Sunday's Premier League clash with Aston Villa, but the hope is that both could recover before the end of the month, potentially in time for the clash with Newcastle on December 26.
Leny Yoro and Ayden Heaven found it difficult without an experienced centre-back alongside them against Bournemouth, and Man United would be a more solid unit with De Ligt and Maguire alongside Shaw, with Lisandro Martinez still short of fitness.
Diogo Dalot has recently been operating as a left-sided wing-back, but Amad's departure for AFCON will force head coach Amorim into a change, and it is difficult to imagine any decision other than Dalot moving across to his more natural side.
Down the left, Patrick Dorgu is the favourite to come back into the team, and the Denmark international will be keen to put down a marker, as it would be fair to say that the defender has still not proven himself since a January switch from Lecce.
There remain loud calls - and T-shirts - asking for Kobbie Mainoo to be introduced into the side, but Casemiro and Bruno Fernandes remain the first-choice midfield duo, and that is unlikely to change at this stage of proceedings.
© Imago / Action Plus
Sesko, Dorgu could benefit from Man United's AFCON absences
Mbeumo's absence from the attacking unit is a major one, with the 26-year-old in strong form for the Red Devils this season, scoring seven times and registering one assist in 17 appearances.
Man United have lost their leading goalscorer midway through the season, which is far from ideal, but Mbeumo's absence will open the door for Benjamin Sesko.
It would be fair to say that Sesko has found it tough in the early stages of his Man United career, only finding the back of the net on two occasions in 13 appearances.
The 22-year-old looked bright off the bench against Bournemouth, though, as he made his return from a knee injury which had seen him miss four matches.
Sesko is likely to now be given a run in the team alongside Matheus Cunha and Mason Mount in the final third of the field, with Joshua Zirkzee another option, although the Netherlands international could potentially leave on loan in January.
Possible Man United XI: Lammens; De Ligt, Maguire, Shaw; Dalot, Casemiro, Fernandes, Dorgu; Cunha, Sesko, Mount