Injuries to Nemanja Matic and Romelu Lukaku mean that Manchester United now only have six players representing their countries over the international break.
Lukaku has joined a number of United players to withdraw from international duty as he pulled out of the Belgium squad for their fixtures with Russia and Cyprus.
The striker underwent an MRI scan to work out the full extent of his injury after missing training with Roberto Martinez’s side on Monday morning.
Lukaku had aggravated a foot injury during United’s victory over Paris Saint-Germain in the Champions League before missing their defeat to Wolves in the FA Cup over the weekend.
Meanwhile, Matic had joined the Serbian national team for their matches against Germany and Portugal but became the latest injury blow for United.
Serbia boss Mladen Krstajic said: “Nemanja Matic will not play in Wolfsburg, nor in Lisbon. He played the last match in the club but did not stay in the field until the end.”
The pair join Luke Shaw, Anthony Martial and Victor Lindelof in withdrawing from their national team squads in recent days, leaving just Antonio Valencia, Marcus Rashford, Paul Pogba, Eric Bailly, Scott McTominay and David de Gea on duty.