Man United manager, Alex Ferguson with new signing, Robin van Persie
Long-term absentee Nemanja Vidic returns for Manchester United, but several other central defenders are unavailable for selection.
Rio Ferdinand injured his groin in training and joins Chris Smalling, Phil Jones and Jonny Evans on the physio's table - Michael Carrick could deputise, reports the BBC.
However, new £24m striker Robin van Persie is expected to make his debut.
For Everton, midfielders Marouane Fellaini and Darron Gibson are doubts with groin and thigh strains.
The injury to Ferdinand is a significant blow to Sir Alex Ferguson's side. It is unclear how long the experienced defender, who United hope will rekindle his successful partnership with Vidic, will be absent for - scan results are expected on Monday.
Smalling is expected to be out for another six weeks after surgery on a broken metatarsal, while Jones is struggling to overcome repeated back spasms.
Evans is the most likely to recover quickest but did not play during pre-season having undergone ankle surgery in May.
The eyes of the football world will be on Robin van Persie when he takes to the turf at Goodison Park. The left-footed Netherlands striker and former Arsenal captain's move from north London to Old Trafford surprised many - United have paid a substantial transfer fee for a 29-year-old, even if he was the Premier League's top goalscorer last season.
Another interesting narrative involves Wayne Rooney, who at the age of 26 is marking 10 years since making his top flight debut. The former Everton youngster played for the Toffees against Tottenham as a 16-year-old. He said at the weekend: "I still feel exactly the same about my football as I did when I made my debut. I'm still fairly young. I just hope I can play for another 10 years."
Plenty are backing Rooney and Van Persie to shine under Sir Alex Ferguson's stewardship, but Everton are expected to unveil their own potentially exciting striking partnership. Croatian forward Nikica Jelavic - who moved to Goodison Park on January transfer deadline day and scored 11 goals in 16 games - should link up well with former Rangers striking partner Steven Naismith. The 25-year-old joined as a free agent in July having scored 28 goals in 98 league appearances while in Glasgow.
Failing to find the back of the net regularly enough has undermined Everton in recent seasons and 24-year-old Kevin Mirallas will add to the club's attacking options.
Unfortunately for his new employer he signed too late to participate against Manchester United, but Everton boss David Moyes is backing his signing: "He'll be a good addition to the squad, he's got a track record, he was an exceptional talent in Greece where he scored a lot of goals and was very exciting over there."
Moyes has lost the services of England international Jack Rodwell, who moved to Manchester City for £12m earlier in the month, as well as long-serving Tim Cahill.
However, he is not short of options in midfield and re-signed Steven Pienaar for Tottenham to bolster his squad. The South African failed to settle in London following his move from Merseyside 18 months ago, and is a popular player in the blue half of the city.
The Toffees will also be determined not to suffer another one of their notoriously poor starts to the campaign.
"Every year it is the same story with Everton," Steven Pienaar has said. "The players tend to wake up in the second half of the season."
An Everton team out of the blocks quickly on Monday could pose a challenge to Manchester United but the visitors still start as favourites.
However, United were also favourites when the two teams last met: Sunday 22 April and a 4-4 thriller that derailed the Red Devils' title chase. What price that scoreline again?