A second-string United side crashed out of the League Cup at Upton Park and with Rio Ferdinand, John O'Shea, Jonny Evans and Rafael da Silva all ruled out, manager Sir Alex Ferguson will be short of defensive options.
The international break came at a good time for the league leaders and at least they should be boosted by the return of captain Nemanja Vidic who emerged unscathed from his comeback game for Serbia.
"It has been a bad spell for us," said Ferguson, adding that injuries were undermining any hopes of emulating the 1999 team who won the treble of Premier League, Champions League and FA Cup.
"It is going to be more difficult than it was in 1999, we didn't have the injuries we do now," he added.
"There is a great desire to do it but we have so many injuries to defenders at present."
United lead the standings on 63 points, five ahead of Arsenal who have a game in hand. United still have to visit Emirates Stadium as well as hosting third-placed Chelsea (54 points) so the league is still wide open.
United, who have won only four of 15 away league games this season, start Saturday's action and will be hoping the game follows a similar pattern as the 4-0 league win at West Ham last season.
West Ham, however, are above the relegation zone on goal difference only and a third home league win a row would boost their prospects of avoiding the drop.
Arsenal, who have to wait until later in the afternoon to play Blackburn Rovers at Emirates Stadium, have won their last seven home games against them, scoring 25 goals in the process.
ANKLE INJURY
Manager Arsene Wenger will hope the knee injury suffered by Robin van Persie playing for the Netherlands is minor but he might not risk his top striker anyway, especially after losing him for the second half of last season after he suffered an ankle injury on international duty.
Arsenal have drawn their last two league games - against Sunderland and West Bromwich Albion - as well as losing in all three Cup competitions.
"I am confident the consistency at the end of the season will be rewarded so let us focus on keeping our unbeaten run going and winning our next game," Wenger said.
Champions Chelsea, who also have a game in hand on United, are not out of the hunt but face a stiff test of their physical resolve at Stoke City.
They could give a place on the bench to midfielder Yossi Benayoun, who played 20 minutes for Israel on Tuesday in his first competitive action since injuring an Achilles in September.
Manchester City, in fourth place on 53 points, host Sunderland on Monday and need to keep winning to shake off Tottenham Hotspur (49) in the battle for fourth.
The Spurs players might be forgiven for having half an eye on next week's Champions League quarter-final against Real Madrid but manager Harry Redknapp will demand 100 percent concentration on
