Manchester United will be looking to continue their mini revival following their Manchester derby debacle, while Sunderland boss Steve Bruce will be hoping to earn his first league victory over Sir Alex Ferguson in 16 attempts.
The Scot celebrates 25 years in charge of the club on Sunday and will almost certainly continue to play Wayne Rooney in the relatively unfamiliar position of central midfield.
The England international, whose mind-set could be altered by the Football Association's decision on whether or not to appeal his three match ban for the European Championships, showed glimpses of his quality against Everton and particularly during the win over Otelul Galati.
Although Ferguson confirmed Rooney's new positioning was only a temporary measure, he indicated injuries to Anderson, Tom Cleverley and Michael Carrick could force his hand at Old Trafford this Saturday.
Darren Fletcher is likely to return following a midweek rest in the Champions League, and the industrious Scot looks set to partner Rooney in the heart of United's midfield. Ferguson must decide on his centre-half pairing with captain Nemanja Vidic likely to return alongside one of Jonny Evans or Rio Ferdinand.
On Friday, Ferguson admitted he was looking forward to seeing a number of familiar faces from Manchester United's illustrious past, most notably Wes Brown and John O'Shea, although the latter is injured. Steve Bruce, Phil Bardsley and Kieran Richardson complete the returning Manchester United alumni.
"They (Brown and O'Shea) were instrumental in a lot of our successes over the years," Ferguson told Sky Sports News.
"They are fantastic professionals. I love both of them in terms of their attitude and loyalty to the club.
"Our association with Sunderland over the years has been interesting,
"Steve has been under a bit of pressure but you only need to lose two games in this game today and you are under pressure.
"He has the mettle for it. He has had to cope with one or two injuries but he will get through that. He will be OK."
Sunderland have not beaten their Premier League counterparts in 18 league games and Steve Bruce will hardly be helped by the fractured nose and eye-socket sustained by Simon Mignolet during the game against Aston Villa last Saturday.
With Craig Gordon still side-lined, third choice stopper Keiren Westwood will deputise and Bruce suggested he had no concerns blooding the former Coventry custodian at Old Trafford.
"Simon had a horrible facial injury, as bad as I've ever seen - and I should know." Bruce told Sunderland's official website. "We wish Simon well and if anyone can come back stronger, it's him."
"Keiren (Westwood) has been knocking on the door, I've told him to be patient and now his chance is just around the corner,
"We couldn't wish for a more able deputy. Keiren is an established goalkeeper who's been itching to play in the Barclays Premier League for years.
"Last weekend didn't faze him and I'm sure the next game won't either."
With John O'Shea injured and Titus Bramble suspended by the club subject to a police investigation, Bruce is likely to retain Michael Turner alongside Wes Brown, who plays his first game against his old club since moving to the Stadium of Light in the summer.
Manchester United: De Gea, Jones, Ferdinand, Vidic, Evra, Valenica, Rooney, Fletcher, Nani, Welbeck, Hernandez
Sunderland: Westwood, Bardsley, Brown, Turner, Richardson, Larsson, Vaughan, Cattermole, Colback, Sessegnon, Bendtner