Erik ten Hag could be without his goalkeeper Andre Onana for as many as seven matches in the New Year after Cameroon qualified for the Africa Cup of Nations.
Cameroon sealed their spot at the tournament in the Ivory Coast by beating Burundi 3-0 on Tuesday to top their qualifying group.
Onana played in the win having returned to the international fold and the £47million stopper is now expected to represent his country at the AFCON, which runs from January 13 and February 11.
If Cameroon go all the way, Onana could miss four Premier League matches against Tottenham, Wolves, West Ham and Aston Villa.
In addition, he could also miss the two-legged Carabao Cup semi-finals and the FA Cup fourth round if United progress that far.
The first Champions League last-16 ties are scheduled for the week after the AFCON final, too, meaning Onana could face a tight turnaround travelling back to England if Cameroon get that far and United reach the knockout stages.
Second-half goals by Bryan Mbeumo, Christopher Wooh and Vincent Aboubakar saw Cameroon to the finals as they topped Group C with seven points, ahead of Namibia.
United signed Onana from Inter Milan this summer but have also bought Altay Bayindir from Fenerbahce and he could step in. Ten Hag also has 37-year-old keeper Tom Heaton in his squad.
Sofyan Amrabat, the midfielder who joined United on loan from Fiorentina on deadline day, is likely to play at the AFCON with Morocco, who qualified back in March.
Winger Amad Diallo could represent hosts Ivory Coast, while midfielder Hannibal Mejbri may play in the competition for Tunisia.
This edition of the AFCON was pushed back from the summer of 2023 due to concerns over the rainy season in the Ivory Coast.
Onana quit the national team after he was sent home from the World Cup in Qatar last December following a fall-out with coach Rigobert Song.
But he confirmed his return to the international fold with a social media message last Monday and then played against Burundi.
United return to action at home to Brighton on Saturday afternoon.