Table-toppers City lead reigning English champions United by five points.
But United, at home to lowly Wolves on Saturday, can cut that gap to just two points with victory at Old Trafford ahead of City's trip to Chelsea on Monday.
While City had the consolation of beating Bayern Munich in their final Champions League match, United's defeat by unheralded Basel will have set alarm bells ringing for Sir Alex Ferguson's side.
And that defeat could be made worse if the knee ligament injury suffered by central defender Nemanja Vidic in Switzerland proves as serious as first feared.
United's fans have taunted arch-rivals Liverpool for having had to compete in the Europa League -- the second tier tournament which both Manchester clubs are now in after finishing third in their respective Champions League groups -- and Ferguson showed little enthusiasm for a competition that is sure to drain his squad's resources.
"It's a competition I've never been in with United," he said.
"It does mean one thing. Thursdays all the way through. Thursday and Sundays. That's got to be dealt with. It's not the best, but that's our penalty for not qualifying."
Ferguson's City counterpart, Roberto Mancini, did not expect the Europa League to have a big impact upon the English title race.
"I think that for the Premier League it changes nothing because both teams are in the Europa League," said Mancini.
"The difference is that the Europa League is harder because we play Thursday and we won't have a lot of time to recover for the games but this will be the only difference."
Arsenal may have lost to Olympiakos in midweek but Arsene Wenger's men had already qualified for the knockout stages of the Champions League.
That, and the failure of the Manchester giants to make it into the last 16, looked anything but likely during the Gunners' stuttering start to the season.
Arsenal, who this weekend celebrate their 125th birthday, will look to make it eight successive Premier League games unbeaten when they face Everton at the Emirates Stadium.
Gunners boss Arsene Wenger again praised striker Robin van Persie who has scored 13 times in his last 10 appearances.
The Dutch forward has suffered a number of fitness problems since his arrival from Feyenoord seven years ago, but he has been injury-free this season and has led by example.
"When you see the player that arrived and the player he is today then you have to give him a lot of credit. His transformation has been exceptional," said Wenger, whose fifth-placed side are still 10 points behind Manchester City.
Saturday's other matches see second bottom Bolton at home to Aston Villa, Liverpool taking on QPR and Norwich up against Newcastle.
Liverpool manager Kenny Dalglish spent the build-up to the game mounting another defence of controversial Uruguayan striker Luis Suarez who is facing two FA charges over his conduct.
"People just jump on the bandwagon and accuse him of this, that and everything else. He's a fantastic footballer and one that every other club would love to have in their side," said Dalglish.
Meanwhile Fulham, fresh from a 1-0 win over Liverpool, travel to promoted side Swansea, while basement club Wigan away to West Brom.
Martin O'Neill's first match as Sunderland manager following the sacking of Steve Bruce sees the Black Cats at home to fellow strugglers Blackburn Rovers while third-placed Tottenham travel to Stoke.
Fixtures (1500GMT unless stated)
Saturday: Arsenal v Everton, Bolton v Aston Villa, Liverpool v QPR, Man Utd v Wolves, Norwich v Newcastle, Swansea v Fulham, West Brom v Wigan
Sunday: Sunderland v Blackburn Rovers (1330GMT), Stoke v Tottenham (1600GMT)
Monday: Chelsea v Manchester City (2000GMT)
Source: AFP
Source: AFP