Manchester United - after securing a Champions League last-16 slot mid-week - will look to drive home their advantage in the English Premier League when they visit Aston Villa on Saturday.
United moved top of the table by beating Arsenal 2-1 last weekend and, with nearest rivals Chelsea and Manchester City both in action on Sunday, victory at Villa Park would put Alex Ferguson's men four points clear.
Having beaten Chelsea and Arsenal in their past two league outings, United have an easier run that includes a trip to Norwich City before home games against Queens Park Rangers and West Ham United.
Wednesday's 3-1 win over Braga in Portugal means Ferguson can afford to rest players in United's two remaining Champions League group games, so the domestic title race will be the priority until the end of the year.
Villa are just one place above the relegation zone, and United striker Wayne Rooney says his side should show no mercy as they bid to stretch their lead.
"There have been games this season where we've been fantastic, and there have been games where we've had to grind out results.
"We're in a good position and we know we can play better football. Now we have a run of games where we feel we can get maximum points so, hopefully, we can do that."
Arsenal's Champions League status is less secure, Tuesday's 2-2 draw at Schalke leaving them in second place in Group A, and last weekend's loss at Old Trafford dropped them to seventh in the Premier League.
Arsene Wenger's side have won just two of their past six EPL games and will be without suspended Jack Wilshere when they host Fulham, who are level on points with Arsenal despite only one win in five.
Arsenal have seen Everton, Tottenham Hotspur and even West Bromwich Albion steal a march on them in the race for Champions League qualification, and Theo Walcott says his team must stand up and be counted.
"It is going to be a tough month for us now," said the England winger. "It is going to test us all, not just physically but mentally as well, and I think we are ready for it."
Everton go into Saturday's visit of Sunderland in fourth place, but hope to end four straight draws, having being denied victory at Fulham last weekend by a 90th-minute goal.
West Brom, meanwhile, will have their work cut out away at Wigan Athletic, who are bidding for a third consecutive victory after wins over West Ham and Spurs.
It could be a decisive weekend for bottom side Southampton, who host Swansea City amid speculation that coach Nigel Adkins' position is under threat after eight defeats in his side's first 10 matches.
Second-bottom Queens Park Rangers take their bid for a first win of the season to Stoke City, while third-last Reading hope to close the four-point gap with Villa when they host Norwich.
In Tottenham's trip to Manchester City on Sunday, the defending champions will seek to bounce back from the 2-2 draw with Ajax that left them hovering above the Champions League trapdoor.
Chelsea would have been in a similar position had it not been for Victor Moses' injury-time winner against Shakhtar Donetsk, which will give the European champions a boost ahead of Sunday's visit of Liverpool.