Nine points clear at the start of the week but only six after Chelsea's 1-0 midweek win at Manchester City, United can ill-afford to slip up at Old Trafford. Prowling Chelsea have a far easier game on paper at home to lowly Sheffield United.
United, who like Chelsea are expected to re-shuffle their side ahead of Monday's FA Cup quarter-final replays, can draw on their recent form and an excellent record against Sam Allardyce's men.
United trounced Bolton 4-0 at the Reebok in October, did the double over them last season with a 6-2 aggregate win and have not lost to them since a 1-0 reverse at Old Trafford in 2002.
However, they will be without Dutch goalkeeper Edwin van der Sar, who has been told to rest a calf strain sustained in the warm-up before last weekend's FA Cup draw at Middlesbrough.
Polish keeper Tomas Kuszczak should again deputise, while striker Alan Smith is hoping to get a rare chance up front.
Smith, who played in the charity match against a Europe XI on Tuesday, is set to get the nod as Frenchman Louis Saha and Norwegian Ole Gunnar Solskjaer are both unavailable and Henrik Larsson has returned to Sweden after his loan spell.
Chelsea were hardly impressive at Eastlands on Wednesday, but there was no doubting their ability to ground out a result and there is likely to be more of the same against Neil Warnock's combative side.
TERRY RETURNS
The other good news in midweek was the return of captain John Terry for his first game since being knocked unconscious in their League Cup final win over Arsenal on Feb 25.
Terry played down an ankle injury picked up in the game at Eastlands, but may yet be spared league duty this weekend.
Chelsea, who face Tottenham Hotspur again on Monday after last weekend's pulsating FA Cup 3-3 draw, will probably rest what players Jose Mourinho can afford.
Arsenal, who moved above Liverpool and into third place with their 1-0 win at Aston Villa in midweek, travel up to Everton.
Liverpool will try to match Arsenal's victory at Villa Park, secured with a side hit hard by injuries and suspensions, when they visit Martin O'Neill's men on Saturday.
Charlton Athletic's bid to avoid the drop continues at home to Newcastle United.
Charlton, 18th in the table, are four points better off than West Ham United and Watford and will be hoping that Stuart Pearce's struggling Manchester City side keep losing.
City, who suffered their fifth consecutive league defeat against Chelsea, are six points better off in 17th place.
They travel to Middlesbrough after newspaper reports that Pearce faced the sack if they lost both this week's games.
