The Reds boss is also keen to rest several first-team players ahead of this Sunday’s derby match with Manchester City in the Barclays Premier League at the Etihad Stadium.
For this season, several fringe players are likely to feature against the Romanian champions at the Theatre of Dreams in a team that should mirror the one which recently lost to Galatasaray.
Due to a lack of wingers, with only Ashley Young fit, United are also expected to reuse the diamond formation that has yielded some success this season, playing in a more direct and narrow manner.
Here, I consider the options available and forecast United’s starting XI for Matchday 6...
David de Gea had appeared to have cemented himself as United’s No. 1 goalkeeper this season, until an operation to have his wisdom teeth removed robbed him of his fitness.
As a result, Anders Lindegaard deputised while the Spaniard was sidelined, but intriguingly, the Dane retained his starting place when de Gea was again available for selection against QPR.
With eyes on Sunday’s Manchester derby, Wednesday’s goalkeeper is likely to miss out on that trip to the Etihad. In keeping with recent events, expect de Gea to start against CFR Cluj.
Sir Alex Ferguson hauled off first-choice right-back Rafael da Silva during the first half against Reading at the weekend, but the Brazilian remains United’s best option and should be rested against Cluj.
In his absence, Chris Smalling is likely to plug the gap following his recent recovery from injury and return to fitness. The former Fulham man has mostly featured in the middle this term, but a lack of options on the right should see his flexibility utilised.
Marnick Vermijl has appeared for the first team this season and might have been considered, but the Belgian youngster played a full match for the reserves on Monday night and is therefore unlikely to feature again just two days later.
Nemanja Vidic is set to make a sensational return against the Romanian challengers, ending a lengthy spell on the sidelines through injury ahead of the Manchester derby.
The Serbian international and United’s club captain is a behemoth presence at the Theatre of Dreams, and his defensive quality has been sorely missed in recent months.
Vida is expected to start on Wednesday and should be replaced midway through the second half as Sir Alex Ferguson hopes to start the club legend at the Etihad Stadium.
Scott Wootton has impressed this season, most notably against Newcastle in the Capital One Cup, and might feature against Cluj after missing the reserves’ draw with Southampton on Monday.
Although Wootton is a similar player to predicted partner Vidic, Sir Alex Ferguson does not want to risk Rio Ferdinand or Jonny Evans and will probably place his trust in youngster instead.
Should he start, Wootton will want to make amends for a late collapse against Chelsea at Stamford Bridge, where his foul contributed to United’s exit from the League Cup.
Signed as cover for Patrice Evra, Alexander Buttner should fulfil his duties on Champions League Matchday 6, given that the Frenchman has already featured in 19 matches this season.
Naturally ambitious going forward, the Dutchman might experience some success against the inexperienced CFR Cluj defence. His defensive work, however suspect, should not be tested.
Sir Alex is likely to rest Darren Fletcher and Michael Carrick—who both started at Reading—and with Anderson unavailable through injury, Phil Jones is expected to feature in midfield.
The England international has been a flexible asset since signing from Blackburn Rovers last summer and would benefit from a combative match in the middle after recently returning from injury.
Jones is likely to sit in the hole in front of United’s defence as part of a diamond formation to break up Cluj’s attacking play whilst helping the Reds maintain possession.
Ryan Giggs is used sparingly by manager Ferguson and, given that he has not featured since last month’s 1-0 defeat at Norwich, the Manchester United legend should start on Wednesday.
As the Reds are currently without any natural width in the absence of the injured Nani and Antonio Valencia, Giggs is likely to play on the left of a flexible midfield diamond.
The Welshman has also been caught off the pace in a number of matches this season and is now something of a luxury player at Old Trafford. He is unlikely to face City at the weekend.
With flexibility and tactical nous, Tom Cleverley is a considerable asset when playing the midfield diamond formation, and his passing ability could prove decisive against Cluj.
The youngster was an unused substitute against Reading on Saturday and, as a result, should feature from the start on Matchday 6. Expect him to come off with the derby just days away, however.
Nick Powell has been one of the major plus points of this season following a selection of admirable performances, most recently in Istanbul, and should start once again on Wednesday.
His attacking endeavours and maturity in possession has seen the 18-year-old feature more regularly in the first team than first thought when signed from Crewe Alexandra in the summer.
With little other than pride on the line against Cluj, Powell could have a field day and don’t be surprised to see his name on the list of scorers should he start.
Javier "Chicharito" Hernandez has rediscovered his top form this season, scoring an impressive nine goals in just nine starts and eight substitute appearances.
However, with Manchester City on the horizon, Sir Alex is likely to rest top strikers Robin van Persie and Wayne Rooney, turning instead to the little Mexican against Cluj.
In light of Robin van Persie’s arrival, Danny Welbeck has been forced to play wide for most of this season. Characteristically, the youngster has been professional and mature, and just getting on with it.
But with van Persie and Rooney both likely to be rested, Welbeck has an opportunity to move into the middle and send out a message against Cluj on Wednesday—his desire to score is huge.
The Reds striker’s flexibility and ability to link midfield and attack is also a huge asset given United’s current lack of width.