Any two of five sides will join West Ham United in relegation from the Premier League on the final day of the season on Sunday when Manchester City are poised to wrap up the third automatic Champions League spot.
Wigan Athletic, Blackpool and Birmingham City are each on 39 points while Wolverhampton Wanderers and Blackburn Rovers on 40 are also still in danger.
Wolves and Blackburn play each other in an intriguing twist (1500GMT) while Blackpool could lose at celebrating champions Manchester United and move out of the drop zone. Equally they could win and still go down given goal differences are so tight.
Wigan travel to FA runners-up Stoke City and Birmingham go to Tottenham Hotspur, who need a win to secure fifth spot and a Europa league berth with Liverpool a point behind and visiting Aston Villa.
FA Cup winners Manchester City lead fading Arsenal by a point in the race for third with fourth only offering a qualifying round slot for the Champions League.
City go to local rivals Bolton Wanderers and Arsenal have a London derby at Fulham.
United is set to field a weakened team to keep its top players fresh for the Champions League final on Saturday against Barcelona.
But even inflicting United’s first home defeat of the campaign might not be enough to save Blackpool, which only rejoined the elite last August after having been relegated from the top division in May 1971.
Blackpool and Wigan, which goes to Stoke, are both in the drop zone on 39 points. Birmingham is only out of danger on goal difference going into its match at Tottenham.
Just a point above Blackpool, Wigan and Birmingham are Wolverhampton Wanderers and Blackburn, who face each other on Sunday, while West Ham has already been relegated.
“One of my analysts was looking at the table the other day. I said, ‘Good God. What are you doing? You are going to go mental,’” Blackpool manager Ian Holloway said. “My dad was an amateur player. He would say, ‘Our name is on the cup.’ Sometimes it is.
“This weekend, we have to do something no one else has managed this season: beat the champions on their own ground.”
Having wrapped up the title with a 1-1 draw at Blackburn last weekend, United is set to rest stars including Wayne Rooney.
“Obviously everybody expects me to leave players out and that will be the case. I have to think about next week,” United manager Ferguson said. “I have to juggle the balls and make sure I get the right mix and keep the right energies for Barcelona.
“There are players who need a game anyway. Darren Fletcher, Paul Scholes and Anderson will all play. So will (Dimitar) Berbatov, (Patrice) Evra and (Edwin) van der Sar.”
Van der Sar will captain the side in his last Premier League match. The 40-year-old Dutch goalkeeper said he will retire after the Champions League final.
Berbatov will get a chance to secure the Golden Boot prize, having been joined on 21 goals in midweek by Manchester City striker Carlos Tevez.
Berbatov has started just four of United’s last 16 games and scored just twice since his double in a win at Blackpool in January.
“The emergence of Javier Hernandez has made it difficult for me to put Dimitar above him,” Ferguson said. “His (Hernandez) performance levels, goals, freshness and pace are fantastic.
“Dimitar understands that. He never complains. He will play on Sunday and hopefully he will be the top goalscorer.”
City, though, will be hoping Tevez scores the goals on Sunday that secure a victory at Bolton, third place and automatic qualification for the Champions League group stage.
Whether the Argentina forward will still be with the FA Cup winners next season remains shrouded in uncertainty.
But manager Roberto Mancini maintained: “Carlos said he wants to stay. Finished. This is history.”
If City draws or loses at Bolton, Arsenal would return to third place with a victory at Fulham and avoid an August playoff to reach the Champions League group stage.
The Gunners have won just two of their last 10 league matches, ending their hopes of winning the title for the first time since 2004.
Arsene Wenger’s side has struggled since a shock loss to relegation-threatened Birmingham in the League Cup final in February.
“The loss of the Carling Cup had a huge impact on the team and we did not handle it well,” Wenger said. “We have enough quality to beat anyone in the world, even with the current squad.
“You have a Champions League final and only one team has beaten both of them — Arsenal.”
Another issue to be resolved on Sunday is fifth place and Europa League qualification.
Tottenham goes into its home match against Birmingham with a one point advantage over sixth-place Liverpool, which is at Aston Villa.
Second-place Chelsea ends the season at Everton, bottom-place West Ham hosts Sunderland and West Bromwich Albion plays Newcastle in a clash of two teams who have survived their first season back in the Premier League.