Arsene Wenger's side sits five points clear at the top of the table but Manuel Pellegrini's men have won all seven of their Premier League games at home this term.
City has made the Etihad Stadium a fortress this season, winning all seven home games in the top flight and scoring 29 goals in the process.
Manuel Pellegrini's side has only conceded twice at home in the Premier League and come into the game on the back of a stunning 3-2 win at Bayern Munich in the Champions League.
Arsenal is five points clear at the top of the Premier League, though, and that advantage would have been even bigger if Everton winger Gerard Deulofeu had not popped up with a late equalizer at the Emirates Stadium last Sunday.
Arsene Wenger's charges suffered their first loss in seven games when Napoli beat them 2-0 in midweek, but they still qualified for the last 16 of the Champions League for the 14th season in a row.
The Londoners' reverse in Italy caused them to drop to second behind Borussia Dortmund in Group F, meaning they will face one of Barcelona, Real Madrid, Bayern, Atletico Madrid or Paris Saint-Germain in the first knockout round.
But Wenger has urged his players to put that disappointment behind them and concentrate on the race for the Premier League title.
"We have done our job now we will give absolutely everything on Saturday morning," said the Frenchman. "We will see what comes out of the draw and will assess that in February, because a lot can change on both sides, on us and the team we play against, so we need to put that to the back of our minds now and focus on the championship."
Arsenal has lost only once on its travels in the top flight this season, the 1-0 defeat at Manchester United in November.
Lukas Podolski could return to the squad after being sidelined since August with a hamstring injury, but Bacary Sagna (hamstring) is ruled out.
Aaron Ramsey will be expected to return to the starting lineup after being restricted to a substitute appearance against Napoli.
City comes into the game brimming with confidence after recovering from 2-0 down to beat European champion Bayern Munich at the Allianz Arena on Tuesday.
That victory was not enough to secure top spot in Group D, but Pellegrini's men have now won five of their last six games in all competitions and know a victory over Arsenal would leave them just three points adrift of their opponent at the top of the Premier League.
Micah Richards sustained a hamstring injury against Bayern so will not feature on Saturday, and former Arsenal fullback Gael Clichy [foot] is a doubt.
Yaya Toure returns after being suspended for the trip to Germany, while Pellegrini must decide whether to give England goalkeeper Joe Hart another chance in the Premier League or keep faith with Costel Pantilimon.