Liverpool tackle Chelsea as a resurgent City play stuttering champions United in the Manchester derby on a crunch weekend of fixtures in the English Premier League.
In the first "big four" clash of the new season, Rafael Benitez's Reds host Jose Mourinho's Blues in an early test of each side's title-winning potential.
And Manchester United head to Eastlands without last season's top two scorers: the injured Wayne Rooney, and Cristiano Ronaldo, suspended for head-butting.
Manchester City, revitalised under former England boss Sven-Goran Eriksson, have the chance to prove their impressive start to the season makes them serious contenders this season.
The Manchester derby, Liverpool's clash with Chelsea and Arsenal's trip to Blackburn take place Sunday.
In tomorrow's matches, league leaders Everton look to keep up their perfect start at Reading.
Big-spending Tottenham, desperate for a first win, host newly-promoted Derby County and West Ham travel to Birmingham with new signing Kieron Dyer set to make his Hammers debut.
At the Madejski Stadium, two of the toughest teams to break down in the Premier League go head to head.
Early pace-setters Everton have got the better of Tottenham and Wigan so far, but they travel to Reading, whose man-marking tactics squeezed a goalless draw out of Manchester United and gave Chelsea a fright before the Blues ground out a win.
Tottenham were tipped to be among the top sides this season but they have lost both matches so far.
"Now there is more pressure to get a result," said Spurs boss Martin Jol's assistant Chris Hughton.
Birmingham have been frustrated in their matches so far, losing 3-2 at Chelsea and succumbing to a disputed last-minute equaliser in a 2-2 draw at home to Sunderland.
They host West Ham, who were embarrassed as visitors Manchester City tore them apart in a 2-0 opening day win.
Newcastle boss Sam Allardyce takes charge of his first league match at St James's Park as the Magpies host Aston Villa.
England striker Michael Owen could make a welcome return for Newcastle, who have not scored at home since February.
However, Villa boss Martin O'Neill wants his defenders to close down the likes of Owen more.
"If we could just tighten up a little bit, especially when we haven't got the ball, then I honestly believe we will start to do better," the Northern Irishman said.
Mido should make his debut for Middlesbrough at Fulham.
Boro lost both their opening games and boss Gareth Southgate cannot wait for the tall Egyptian striker to get started.
"You want a centre-forward to hold the ball up, to be a physical presence and to score goals. Mido brings all of those attributes," he said.
Roy Keane's Championship winners Sunderland travel to Wigan looking to capitalise on their four points from six games so far, with new striker Michael Chopra scoring in both games.