
Arsenal, one point ahead, face a tricky trip to face Portsmouth, while champions United go to Sunderland where they will meet a side led by their former midfield star Roy Keane.
With 43 points from 18 games and just one defeat, Arsenal are looking strong at the top and manager Arsene Wenger is delighted to be top of the table at Christmas.
"Maybe I am a very optimistic man but I always have great belief in my team," Wenger said after Arsenal's 2-1 win over Tottenham on Sunday.
"We can keep getting results. We played a top level game last week against Chelsea and we maybe relaxed a bit after that.
"But we still have 43 points with 20 games to go so we are in a very strong position. You can argue with the points we got today but all the rest, we have got what we deserved."
United have been keeping pace with Arsenal and the two sides have opened up a five-point gap at the top.
Manager Sir Alex Ferguson has a couple of injuries, with Rio Ferdinand and Edwin van der Sar out, and the Scot hinted that he will rotate his side against Sunderland, who are languishing in the bottom three.
"We have started the Christmas period well and I will freshen things up a bit on Wednesday," Ferguson said.
"I have players like Darren Fletcher, John O'Shea, Nani, Louis Saha and Park Ji-sung, who is back in the squad now. They are all fit and fresh so we've got a few options."
Chelsea, who lead the chasing pack, look likely to be without goalkeeper Petr Cech for the visit of Aston Villa.
Cech injured his hip against Everton on Sunday and with Carlo Cudicini also struggling with a rib injury, Hilario, who came on against Everton, looks set to start.
"I cannot say it will be easy if we lose Cech," said Chelsea manager Avram Grant, who is already without captain John Terry for at least another month.
"To play for so long with so many injured for a long time, I don't like it. But I cannot do anything about it. It's fact, and we need to get through it as soon as possible like we have done in the last three months."
With Manchester City not in action until Thursday, against Blackburn Rovers, Liverpool can leapfrog them into fourth with a win at bottom side Derby County, who are six points adrift at the foot of the table.
Liverpool, who have a game in hand on the top four, are coming off a 4-1 win over Portsmouth, and could have Xabi Alonso back for his first start since returning from a foot injury.
Sixth-placed Everton will be out to bounce back from their narrow loss to Manchester United by beating an improving Bolton side.
Wigan Athletic, who sit second-from-bottom, will be eyeing victory when they host a Newcastle United side who could only draw with Derby County on Sunday.
Tottenham Hotspur will hope to continue their steady climb up the table after their poor start to the season by beating another struggling side, Fulham, at White Hart Lane.
Birmingham City face Middlesbrough and West Ham United take on Reading in the day's other match.
By Ben James, dpa