Arsene Wenger's side head to Eastlands still reeling from a 2-0 defeat against Napoli on Wednesday which could prove a fatal blow to their hopes of winning the Champions League.
It was a major setback just days after a frustrating 1-1 draw against Everton stopped Arsenal opening up a seven-point lead at the top of the Premier League.
However, Wenger's thoughts are focused firmly on what he thinks is a perfect chance for his side to build a nine-point lead over the side many view as Premier League title favourites.
"Let's not forget that if you are in City's position and they lose, then they're nine points behind, so they have more negative pressure than we have," Wenger told a news conference on Friday.
"We have a positive pressure that we can make a big difference with them, so let's look at it like that."
Meanwhile, Germany centre-back Mertesacker knows the critics are once again starting to question whether Arsenal have the mental strength to overcome the psychological scars of the club's eight-year trophy drought.
"Now everybody is questioning our group and asking if we can maintain that level, so we have to stay together and think that 'yes, we are strong enough'," said Mertesacker.
"It is always difficult, especially after 15 games in the league and with the Christmas period coming.
"You think you have a good chance to achieve something this season, but you have to keep your momentum and that is really important."
While Arsenal hope to cement their position at the top, fourth-placed City cannot afford to lose their 100% home record if they want to stay in touch with the leaders.
Mourinho looks to pep up misfiring Chelsea
Jose Mourinho is desperate to fire up his shot-shy strikers when Chelsea return to Premier League action against Crystal Palace at Stamford Bridge on Saturday.
The club's three main forwards, Fernando Torres, Samuel Eto'o and Demba Ba, have managed just four league goals between them this season.
And Blues boss Mourinho has already expressed his frustration at his side's lack of cutting edge in front of goal, which was again apparent in last weekend's 3-2 defeat at Stoke.
Saturday's Fixtures
Man City v Arsenal
Cardiff v West Brom
Chelsea v Crystal
Everton v Fulham
Newcastle v Soton
West Ham v Sunderland
Hull v Stoke
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i like win from arsenal tomorro