Before all eyes turn to Monday's crucial Manchester derby between the league's top two, Arsenal, Newcastle and Tottenham take the pitch knowing a fourth-place finish may no longer be enough to qualify for Europe's premier competition.
If Chelsea beats Bayern Munich on May 19 to capture a first Champions League title and don't finish in the top four of the Premier League, the team that finishes fourth will play in next season's Europa League.
Arsenal looked sure of securing third but picked up just one point from home matches against Wigan and Chelsea last week to give in-form Newcastle and out-of-sorts Tottenham renewed hope of catching Arsene Wenger's side.
"They were really good chances to put ourselves into third place comfortably. At the moment we still have to fight for third place," said Arsenal defender Thomas Vermaelen, whose team visits Stoke on Saturday.
"It is not going to be easy, but that is because you play in England and it is not an easy league. Everybody can beat everybody ... It is going to be tight, but it is going to be interesting."
Sparked by the goals of striker Papiss Demba Cisse, Newcastle is the form team in the division after a spectacular run of seven straight wins heading into Saturday's match at relegation-threatened Wigan.
Newcastle is fourth, three points behind Arsenal with a game in hand and three ahead of an ailing Spurs team that has won just one of its last nine league games.
Tottenham, whose dip in form has coincided with manager Harry Redknapp being linked with the vacant England job, hosts next-to-last Blackburn on Sunday to kick off arguably the easiest run-in of the Champions League hopefuls.
"Of course we can turn things around," Tottenham captain Ledley King said. "There are still four games to play, all winnable games if we perform to our capabilities."
Chelsea, meanwhile, may have to win the Champions League if it is to qualify for next season's competition.
Roberto Di Matteo's team is sixth, four points behind Newcastle, going into Sunday's home match against west London rival Queens Park Rangers but is full of belief after eliminating the mighty Barcelona in the Champions League semifinals.
"We don't want to look forward too much — we are not finished yet, we are not safe in the league for the Champions League place," said defender Branislav Ivanovic, one of four Chelsea players who will miss the Champions League final because of suspension.
"We want this still (and) we are in the final of the FA Cup. So, there are a lot of things to do. We've got a big squad and we'll try to do everything."
It is also a huge weekend for the teams looking to avoid joining Wolverhampton Wanderers in being relegated to the League Championship.
Blackburn, which is three points from safety, is in most danger but third-bottom Bolton's hopes of staying up were boosted by a 2-1 win over Aston Villa on Tuesday.
Bolton travels to midtable Sunderland on Saturday lying one point behind Wigan and QPR. Villa, which is away to Midlands rival West Bromwich Albion, is two points further clear but has been dragged into the relegation battle.
Also on Saturday, seventh-place Everton hosts Fulham needing a victory to keep Liverpool at arm's length, with two points separating the Merseyside teams.
Liverpool visits Norwich and will be without midfielder Charlie Adam, who will miss the remainder of the season — including the FA Cup final against Chelsea — with a knee injury.
Swansea is at home to Wolves in the other match.