Both sides are making their respective debuts in the elite European competition and have been drawn together in Group A.
Looking ahead to the clash at Etihad Stadium, Mazzarri believes his side are on a roll after their 3-1 win against Cesena in the Serie A and have what it takes to upset the big spending Citizens.
"There's no doubt about the challenge posed by the opposition but after the confidence-boosting away win at Cesena, we are determined to put up a fight," Mazzarri said according to La Gazzetta dello Sport.
"My players must not think about the fact that this is the Champions League or who the opponents are.
We did well against Villarreal and Liverpool at grounds that are no less difficult than this one, and when we were less experienced. We can repeat that.
"We're here to give Manchester City a game and to make life tough for them, as we did with most teams in Italy and around Europe last year.
"Of course, with the star quality they [Manchester City] have we must be careful not to allow them too many chances, which is what happened at Cesena."
The Italian coach conceded his side are the underdogs in the group, but insists they should be proud to be playing at the highest stage.
"The ranking says that we're the bottom team in this group. We haven't played in this competition for 21 years but we're on an upwards curve now.
"We can be proud of what we're doing and we'll take on City as if this were a final. They've spent a lot on transfers in recent years and brought in players with lots of international experience. Yet we finished third in the league just as they did. That's the beauty of football."
Napoli and City will also have to contend with German giants Bayern Munich and Spanish outfit Villarreal for qualification from Group A of the Champions League.