Manchester United, Chelsea, Arsenal and Liverpool switch their attention away from European glory and back to the English title race at the weekend.
Champions and current league leaders United, who beat AS Roma 2-0 in the Champions League on Tuesday, will face Middlesbrough on Sunday, hoping Manchester City had done them a favour a day earlier by inflicting defeat on Chelsea.
The London side urgently need the points to keep up their title challenge as well as to revive their spirits after a 2-1 defeat in the Champions League at Fenerbahce on Wednesday.
Arsenal and Liverpool, who battled to a 1-1 stalemate in the Champions League at the Emirates Stadium on Wednesday, meet again at the same venue on Saturday with league points at stake.
With six matches to play United lead the standings with 76 points, five clear of Chelsea (71), who are a point ahead of Arsenal (70) with Liverpool in fourth place on 62 points.
United are in outstanding form in the Premier League, where they have won their last four matches without conceding a goal.
Boro's Brazilian striker Afonso Alves hopes to enjoy a change in fortune when the sides meet at the Riverside.
The 12 million pounds ($23.79 million) January transfer window signing missed a sitter and struck the woodwork twice in a 1-0 defeat by Chelsea last week and is yet to score for his new club, who still need points to ensure safety.
Complacency will not be a factor for United, as manager Alex Ferguson knows one slip could allow the chasers to close the gap in the title race.
Nemanja Vidic is unlikely to play after being injured early on in Rome so Mikael Silvestre could return after being out since September with a cruciate knee ligament injury.
Chelsea, who thumped Manchester City 6-0 at Stamford Bridge in October, have not lost in 15 league matches and must fancy their chances against a City side whose bright start to the season is now just a distant memory.
City have two wins in their last 11 league matches.
After their Champions League draw on Wednesday, Arsenal and Liverpool will be keen to pick up all three points on Saturday. Arsenal are still chasing the title while Liverpool are keen to keep fifth-place Everton at bay.
Liverpool boss Rafa Benitez said the Champions League draw at the Emirates would have no influence on what happens on Saturday.
"None at all," he said.
"Different competition, different points at stake and it will have no bearing on what happens."
Liverpool face Arsenal in the second leg of their Champions League clash at Anfield next Tuesday.
At the other end of the table, with bottom club Derby County already relegated, it is approaching make or break time for the two other clubs occupying relegation spots.
Fulham, six points adrift of fourth from bottom Birmingham City with just six games to go, face a "must win" match at home to Sunderland.
Bolton Wanderers are at Aston Villa while Wigan Athletic manger Steve Bruce hosts his old club Birmingham. Everton host doomed Derby on Sunday.