The Red Devils may have seen Cristiano Ronaldo and Carlos Tevez depart for pastures new this summer, but Sir Alex Ferguson has brought in Antonio Valencia and Michael Owen to bolster his squad.
United remain the team to beat as they bid to make history on two fronts in becoming the first team to be crowned champions four years on the trot, and overtake fierce foes Liverpool as the most successful side in the English league.
For Birmingham, an opening weekend trip to Old Trafford represents the toughest possible examination of their top-flight credentials having secured promotion from the Championship.
And their Premier League record at the home of the Red Devils leaves much to be desired, with no points and no goals from their five previous visits.
But Ferguson's men are not always the fastest starters in the top-flight marathon, having been held on home turf by Newcastle and Reading on the opening day of the past two campaigns.
Team newsNani confirmed he had made a rapid recovery from the shoulder injury he sustained in the Community Shield against Chelsea with a substitute appearance for Portugal against Liechtenstein on Wednesday.
Goalkeeper Edwin van der Sar is out after finger surgery so Ben Foster continues to deputise despite pulling out of the England squad in midweek, while inspirational centre-back Nemanja Vidic is out with a calf problem.
Jonny Evans would be the first choice to replace the Serbia international, but he missed Northern Ireland's encounter with Israel this week after suffering an ankle injury.
Wes Brown should be available but has not played for over a fortnight since injuring a thigh during a pre-season tournament in Munich.
Craig Cathcart could be drafted in, while Ferguson would also have the option of using John O'Shea in the centre of his defence and allowing Ritchie De Laet to build on his Premier League debut at Hull City last term.
Blues boss Alex McLeish faces major selection problems with defenders Liam Ridgewell, Martin Taylor, Scott Dann, Giovanny Espinoza and David Murphy all unavailable.
Midfielder Lee Bowyer is suspended while striker Marcus Bent is sidelined by a hamstring problem.
New signings Joe Hart, Roger Johnson, Gregory Vignal and Barry Ferguson will all make their debuts, while fellow new boy, striker Christian Benitez, could be on the bench as he continues his recovery from shoulder surgery.
Possible starting XIs:Man Utd: Foster, Brown, Evans, Ferdinand, Evra, Carrick, Fletcher, Nani, Park, Berbatov, Rooney.
Birmingham: Hart, Carr, R Johnson, Queudrue, Vignal, Larsson, Carsley, Ferguson, McSheffrey, Jerome, Phillips.