Pep Guardiola's men travel down to London to lock horns with Premier League pace-setters Chelsea in Saturday's lunchtime kick-off (12:30pm).
Our opponents are yet to concede on home soil in the league this season, winning both of their matches at Stamford Bridge by a 3-0 margin against Crystal Palace and Aston Villa respectively.
However, City's recent record makes for equally impressive reading, with four successive clean sheets and a total of 23 goals scored in the past six matches in all competitions.
FPL players have been spoiled for choice when deciding on which Chelsea and Manchester City stars to recruit for their respective squads, but which way will the balance tip when the Premier League holders face the European champions?
As part of our regular series, the Scout provides expert analysis into a City star expected to thrive, an opponent to keep your eye on and another Premier League player they're backing to pick up the points this weekend.
Matchday Live host Natalie Pike also offers her thoughts ahead of Saturday morning's 11:00am deadline.
Check out who the Scout and Natalie have chose in our Gameweek Six predictions below...
The Scout: The return to action of Kevin De Bruyne (£11.9m) against Leicester City last weekend could prove decisive for Manchester City at Stamford Bridge.
After stepping up his form and fitness with a goal and a 90-minute runout in the midweek EFL Cup win over Wycombe Wanderers, the Belgian’s 1.5% ownership makes him an outstanding differential in Fantasy.
City’s playmaker claimed a 13-point return away to Chelsea in Gameweek 17 last term, scoring once and supplying an assist in a 3-1 win.
Natalie's Matchday Live pick: Joao Cancelo (£6.0) has played in all five Premier League games so far and that’s likely to continue seeing as he had a break in midweek.
We’ve conceded just one goal in the Premier League so far and he’s a big part of that, but also what is so important about Cancelo is that he does get assists, make key passes and at some point will get a couple of goals.
He’s a safe bet in my opinion for someone who’s going to start, and might get some extra bonus points.
Opponent to watch
The Scout: Romelu Lukaku (£11.7m) will be the main threat for Chelsea.
The Belgian has scored four goals in five matches since returning to the club, including a 13-point haul against Aston Villa in his last home appearance.
Natalie's Matchday Live pick: Antonio Rudiger (£5.6) is a solid choice, Chelsea have also only conceded one goal so far in the Premier League like us. He also got on the scoresheet last week and clocked up a load of bonus points as well.
Romelu Lukaku on the other hand is a world class striker, Chelsea really made a statement when they signed him.
I’m reluctant to say Rudiger because I think we’re going to score, and I’m reluctant to say Lukaku because we could keep a clean sheet!
Premier League Pick
The Scout: Mohamed Salah (£12.6m) and Cristiano Ronaldo (£12.7m) are expected to be the top captaincy picks for Gameweek six.
Salah visits Brentford as the top-scoring player in Fantasy on 50 points, scoring four goals and supplying three assists in his first five outings.
Ronaldo, meanwhile, hosts Aston Villa having produced two goals and 13 points in his previous home match.
Natalie's Matchday Live pick: Newcastle's Allain Saint-Maximin (£6.7) had a great game against Leeds last week, grabbing his team’s equaliser at St James’ Park.
He’s already scored a couple this season and statistically he’s getting a lot of chances, he’s having a great season so far.
He’s also relatively cheap for a striker, and Newcastle have some favourable fixtures coming up.
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