Everton, with two wins out of two, will be hopeful of making it a perfect nine points when they travel to Reading.
But the biggest action of the weekend will be on Sunday at Anfield and Old Trafford.
Chelsea, joint top with Everton and Manchester City from two wins, face a Liverpool side who have begun the season well, beating Aston Villa in the League and then winning a Champions League qualifying leg at French club Toulouse in midweek.
Jose Mourinho's pledge that Chelsea will play a more expansive style this year has been seen on the pitch in their 3-2 win over Birmingham and 2-1 win at Reading.
They should be boosted by the likely return of captain John Terry, but Liverpool are sweating on the fitness of their own skipper, Steven Gerrard, who went off in the Champions League qualifier against Toulouse on Wednesday after receiving a stamp on his foot.
Liverpool manager Rafael Benitez must choose who to play in attack - Fernando Torres and Dirk Kuyt started against Villa while Andriy Voronin and Peter Crouch joined forces in Toulouse.
Manchester City manager Sven Goran Eriksson will be hoping his side makes it three out of three when they play Manchester United at Old Trafford.
But United will be smarting after two draws and also after being on the wrong side of some derby defeats in recent times.
Sir Alex Ferguson's side will be without the injured Wayne Rooney and the suspended Cristiano Ronaldo, but Ferguson said he was hopeful that the presence of new signing Carlos Tevez can inspire his team to victory.
"He was absolutely terrific," Ferguson said after the draw with Portsmouth on Wednesday. "He made a great contribution, hopefully he's fit and ready for Sunday.
"We're going to be missing Wayne Rooney and Cristiano Ronaldo for the derby. But the good thing is that I got 90 minutes out of Carlos. He tired in the last 15 minutes but I couldn't take him off because he is capable of scoring from any situation whether he is tired or not."
Everton can go three points clear for a while at least if they win at Reading, while at the other end of the table, Tottenham Hotspur (home to Derby) Bolton Wanderers (away to Portsmouth) and West Ham United (away to Birmingham) will be hoping to win their first points.
Arsenal will be out for a second straight win when they travel to Blackburn Rovers, while Fulham meet Middlesbrough, Newcastle face Aston Villa and Wigan Athletic take on Sunderland.