The southern Italians host the west Londoners at the San Paolo stadium tomorrow in the first leg before a trip to Stamford Bridge in three weeks' time. While Chelsea are in disarray, suffering a number of underwhelming performances and results, Napoli have just rediscovered their own form.
"We're happy to be here and playing a two-legged tie against a Chelsea who have played more than 100 [Champions League] matches and that says a lot," Mazzarri told reporters. "But it seems strange to me to say that we are favourites. We have to try to do our best, as we have always done in these situations."
Napoli have been inconsistent throughout the season and currently sit down in sixth in Serie A. Impressive victories against AC Milan, Inter Milan and Manchester City have been followed by defeats and indeed far too many draws.
But they beat Chievo and Fiorentina in their last two league games, in which they started to look like the team that thrilled Italy last season with their unexpected title challenge.
Chelsea, on the other hand, come into the game having been held to a 1-1 draw at home by Championship side Birmingham City in the FA Cup. And that after a 2-0 defeat at Everton and blowing a 3-0 lead in a draw with Manchester United.
They have also drawn with newly-promoted pair Norwich City and Swansea City in recent weeks, leaving coach Andre Villas-Boas under pressure with his team outside the top four in the league.
"We hope they're not at their best because they have many decisive [players]," said Mazzarri. "But that doesn't mean we change our logic or application, we need to defend well so we can counter.
"This match is like a derby, it escapes all logic and form-guide, and let's not forget that they have great qualities. The devlopment of our players has been incredible over these last few years.
"Playing the perfect match means performing above ourselves and then we hope things will go our way. The important thing is not to concede. We don't have much experience [of that] so it's important that we start off well defensively."
Italian teams are improving
Chelsea represent England's last realistic hope of having a team in the Champions League quarter finals, with City and United falling at the group stage and Arsenal virtually out having been thumped 4-0 in their first leg against Milan.
But Mazzarri, whose side eliminated City in the group stages, believes the big difference is Italian sides are improving rather than the English getting worse.
"Arsenal are in a construction phase but it is Italian football that has changed rather than English football," said Mazzarri. "There won't be much tactical difference between Chelsea and City.
"For me preparing for Chelsea is like preparing for Chievo. I've been used to preparing ever more important matches for many years because I started at the bottom. Tactically Cheslea have recently used 4-4-2 as well as 4-3-3, we've tried to study them well."