Manchester United are on the verge of suffering an injury crisis at the start of the busiest period of the campaign after Robin van Persie, Michael Carrick and Danny Welbeck were all forced to withdrawn from international duty through injury.
Van Persie has pulled out of Netherlands' squad to face Japan and Colombia with groin and toe problems while Carrick and Welbeck are out of England's squad against Chile and Germany with respective knee and Achillies injuries.
Carrick came through United's win over Arsenal but Van Persie was substituted on 80 minutes after scoring the eventual winner but Welbeck hasn't played for the club since the October win over Stoke City.
The trio join an injury list which includes Nemanja Vidic, who has left hospital after being concussed following a collision with David de Gea in the 1-0 win over Arsenal, as well as full back Rafael and midfielder Darren Fletcher.
With each player not featuring during the international break, all six players are considered doubts for the start of the busiest period in the season. United face 11 games in less than five weeks starting against Cardiff City on 24 November.
Fixtures include the Premier League trip to Tottenham Hotspur, the climax to the club's Champions League campaign and the League Cup quarter final against Norwich City.
Fletcher has only recently returned to training but played 90 minutes against Fulham for the United Under-21's earlier this month ahead of his return to first team duties.
Rafael played in the win over Fulham but missed the visit of Arsenal with a foot problem and is set for a lengthy spell on the sidelines.
Meanwhile, United staff are expected is be cautious regarding Vidic's fitness, after he was replaced at half-time against Arsenal and receiving a heavy blow after being accidently struck by De Gea at Old Trafford.
Since Tottenham's mishandling of Hugo Lloris, with the French goalkeeper allowed to play on despite being knocked unconscious against Everton, scrutiny over the manner in which clubs deal with head injuries has swelled.
Vidic went to hospital but has since been released after making a full recovery, but will be monitored by United staff and could be rested for the trip to Cardiff.