With United unable to sign a replacement, the pressure will be on 21-year-old England forward Marcus Rashford to deliver the goals in a more central role than he has previously operated in.
Tim Sherwood's hopes of becoming Tottenham Hotspur's next permanent manager were boosted after his attacking team came back to win 3-2 at stuttering Southampton in an enthralling Premier League encounter on Sunday.
Tottenham Hotspur's England duo Harry Kane and Dele Alli fired them to a comfortable 2-0 win over mid-table Watford that cemented their place in the top four at Wembley on Monday.
Tottenham Hotspur's exhilarating Premier League title surge came to a shuddering halt as they lost 1-0 at West Ham United on Friday to leave Chelsea needing six points from four games to be crowned champions.
But for third-placed Spurs, who trail leaders Manchester City and Liverpool by five points, this may prove to be a loss that leaves them with too much ground to make up.
City's dream of a quadruple of titles ended with their away-goals loss after Wednesday's second-leg ended with a 4-3 win, but a 4-4 aggregate score.
West Bromwich Albion have ruled out the prospect of Saido Berahino leaving the club during the current transfer window, leading Tottenham Hotspur manager Mauricio Pochettino to compare his club's pursuit of the striker to a frustrated love affair.
Following is a match by match look at the English Premier League's weekend fixtures
'I've been here 20 years and many times had the opportunity to leave. I don't have to convince you my preference has always been Arsenal'
English Premier League leaders Manchester City and Chelsea slugged out a magnificent 4-4 draw at Stamford Bridge.
It is a mark of how far Tottenham Hotspur have come that they start as favourites to win what could be a pivotal Champions League Group E fixture away to Bayer Leverkusen on Tuesday despite the absence of key defender Toby Alderweireld.
Barcelona coach Ronald Koeman has defended centre-back Gerard Pique's right to make comments about referees favouring Real Madrid.
Tottenham Hotspur's hopes of a first victory over Chelsea at Stamford Bridge in 26 years disappeared as a 2-2 draw left Leicester City celebrating the Premier League title on Monday.
Rashford put United ahead in the seventh minute
Liverpool belatedly kick-started their year and damaged Tottenham Hotspur's slender Premier League title hopes as Sadio Mane struck both goals in a 2-0 victory at Anfield.
Tottenham Hotspur needed a 73rd-minute Andros Townsend penalty to end the dogged resistance of visiting third tier Sheffield United and secure a 1-0 lead in their League Cup semi-final first leg on Wednesday.
Tottenham Hotspur lost their cool and their Premier League title hopes as they let slip a two-goal lead at Chelsea to draw a stormy London derby 2-2 on Monday.
West Brom's Dawson is villain and hero as Spurs' chances at League title fades; Leicester now need just one win from three games to claim EPL crown
Liverpool's Raheem Sterling netted a sharply-taken double in a 3-1 win over Bournemouth on Wednesday to set up a League Cup semi-final with Chelsea.
"Harry Kane, he's one of our own," Tottenham Hotspur supporters sing in praise of the 21 year-old striker from Chingford, the London suburb where David Beckham learnt his football.
Strong start bodes well for Spurs' title hopes, says Lee
Eriksen punctured Brighton's armour from Tottenham's 29th goal attempt -- 21 of which were from outside the penalty area.
Images from the English Premier League matches played on Sunday night.
Arsenal have only lost six times to Tottenham Hotspur in 43 matches since Arsene Wenger became their manager nearly 18 years ago, but the Frenchman is taking nothing for granted before the first north London derby of the season on Saturday.
Tottenham manager Mauricio Pochettino has said Ajax have an unfair advantage because the whole of the Dutch league programme was postponed to help Erik ten Hag's side prepare.
Manchester City host Tottenham Hotspur on Saturday on the back of a record 15 successive English Premier League wins, and on the basis of their visitors' recent away form, a 16th victory appears to be the likely outcome.
It took Harry Kane four years to become an overnight sensation at Tottenham Hotspur and with a Young Player of the Year award as a full England international.
Tottenham Hotspur took a large bite out of Leicester City's Premier League lead with two goals apiece from Harry Kane and Dele Alli earning them a 4-0 victory at Stoke City on Monday.
The 46-year-old Norwegian has guided United to 14 wins in 19 matches in all competitions as caretaker boss since replacing the sacked Jose Mourinho in December.
Alex Ferguson famously described the Premier League title run-in as 'squeaky-bum time' and leaders Leicester City and second-placed Tottenham Hotspur look best-placed to handle the pressure.
As Manchester City fans left Goodison Park after a 2-0 victory over Everton on Wednesday that sent their team back to the top of the Premier League, they aimed their chants across adjacent Stanley Park to title rivals Liverpool.
Despite their first-leg advantage, Pochettino warned against complacency and said he wanted his team to play for another win, although they have had one day less to prepare than the Germans.
Following is a match by match look at the English Premier League's weekend fixtures.
Following is a match by match look at the English Premier League's season-opening weekend fixtures:
IMAGES from the Premier League matches played on Saturday
Rediff.com brings you the previews of the main matches scheduled for this weekend in the English Premier League.
Riyad Mahrez struck twice as Manchester City reached the Champions League final for the first time thanks to a 2-0 victory over Paris St Germain at the Etihad Stadium on Tuesday that secured a 4-1 aggregate win.
With less than a month of the Premier League season left it remains Chelsea's title to lose but Tottenham Hotspur defiantly stayed in contention by grinding out a 1-0 victory at Crystal Palace on Wednesday.
Tottenham Hotspur endured a night of frustration against London rivals West Ham United but were spared a shock defeat as Son Heung-min salvaged a 1-1 draw with a stunning late equaliser at Wembley on Thursday.
Lucas Moura scored twice as Tottenham Hotspur romped to a 3-0 English Premier League win over Manchester United at Old Trafford on Monday as Jose Mourinho's team's defensive frailties were brutally exposed once again.
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