Sir Alex Ferguson's United last won in the league at Stamford Bridge 10 years ago and the rivalry between the clubs burns as fiercely as ever, despite the 12-point gap that currently separates the two sides.
United are locked in a battle with their near neighbours Manchester City at the head of the table, while Chelsea's immediate challenge is to tighten their grip on fourth place.
John Terry will miss the game with a knee injury but while the fall-out from the Football Association's decision to strip him of the England captaincy has overshadowed Chelsea's preparations, Ferguson is well aware of the challenge posed by Villas-Boas' side.
"It's not an easy game going to Stamford Bridge. We haven't beaten them since 2002, which is a decade," said the United manager.
"In that period, Chelsea's rise to prominence has been obvious and the last seven years, we have battled with them for league titles. Therefore, you expect a hard game and it will be.
"I hope our form will stand up as it did in the Arsenal game. Even last week at Liverpool (in the FA Cup), it was a really good performance from us, we just threw the match away with two bad mistakes.
"We didn't deserve it, but that can happen in a cup tie."
But Villas-Boas warned a Chelsea victory could derail United's title bid -- just as their win over City last December had triggered a dip in form for Roberto Mancini's side.
"The leader in mid-December, Man City, was undisputed but they lost against us and continued to lose games and continued to drop points," said the Chelsea manager, who knows three points would strengthen his position after a week in which Jose Mourinho was linked with a move back to the club.
"Man United in the last five games have three wins and two defeats, surprisingly, and that is the situation of the league and we can never tell."
Terry's absence could mean a first start for Gary Cahill, while Frank Lampard could return after a calf injury.
Midfielders Ramires and John Obi Mikel are injured.
Ferguson still faces an anxious wait over his goalkeeping position, with Anders Lindegaard expected to be out for up to six weeks with ankle ligament damage and David de Gea also facing a late fitness test on his own ankle injury.
Ferguson expects de Gea, who has found his introduction to English football a torrid one, to recover in time to play, meaning young Englishman Ben Amos -- who made his league debut in the 2-0 mid-week victory over Stoke -- will be on the bench.
"De Gea should be fit," said Ferguson. "In fairness to Ben Amos, he has been agitating for this opportunity for quite a while and we had to calm him down in the sense of whether he should go out on loan or not.
"It's not easy if you're in Europe to let one of your goalkeepers go. You do really need three of them, that point's been proved now.
"Ben did well the other night. He has had opportunities in the League Cup, played against Valencia, things like that.
"He's had a little bit of experience but not the kind of experience you'd expect going into a game like Stamford Bridge. It is something I will make a decision on later."
However, the injury news is almost entirely positive for Ferguson elsewhere as Wayne Rooney, Nani, Ashley Young and Tom Cleverley will all be in the United squad.
"Obviously Young has been out a few weeks, Cleverley has been out a few months so it's more likely Thomas will play against Chelsea reserves on Monday, but he's travelling anyway," explained Ferguson.
"Hopefully, Nani is okay. He has trained the last two days."
Source: AFP
Source: AFP