Last season's runners-up top the group after one game, while Napoli could only manage a goalless draw with Red Star Belgrade on matchday one.
In a group which also includes Paris Saint-Germain and Liverpool, it is not ideal to start a campaign with a goalless draw against Red Star Belgrade - the easiest of the opponents on paper.
Champions League trips to Eastern Europe are notoriously difficult, but that stalemate last month leaves Napoli realistically needing to take more points off the two group favourites if they are to progress into the knockout stages for only the fourth time ever.
Napoli have been steadily growing as a force in Italian football over recent years and last season only narrowly missed out to Juventus in their bid for a first Serie A title since the days of Diego Maradona, but they are yet to translate that improved form to Europe.
The last 16 is the furthest the Partenopei have ever made it in this competition - be it the European Cup or the Champions League - and the draw has made it difficult for them to even make it that far this time around.
A victory over last season's beaten finalists would be a statement that Napoli are a force to be reckoned with this season, though, and they have one of the Champions League's greatest ever managers leading them too.
Carlo Ancelotti is one of only three managers - along with Liverpool's Bob Paisley and Real Madrid's Zinedine Zidane - to have won this trophy three times, and Napoli are the eighth different club he has led in the competition throughout his illustrious coaching career.
Even so, the priority will still be ending a 28-year wait for a domestic title - Napoli's last came in the same year as Liverpool's, incidentally - and that already looks unlikely courtesy of a defeat to league leaders and seven-time defending champions Juventus on Saturday.
Napoli squandered a lead in Turin en route to a 3-1 defeat, leaving them already six points adrift of their title rivals after just seven games of the season.
Gli Azzurri have not lost back-to-back matches since early December and are unbeaten in their last eight outings at home, but they have also lost two of their last three European outings at the Stadio San Paolo - including one at the hands of Manchester City in last year's group stages.
That result was their first ever home defeat to English opposition, though, while they have lost only four of their last 26 European outings at home, winning 16 of those.
Recent Champions League form: D
Recent form (all competitions): LWDWWL
Liverpool are no longer perfect, but the feelgood factor still surrounds the Anfield outfit despite a week which has seen them lose and draw with fellow title hopefuls Chelsea.
A 2-1 home defeat to the Blues in the EFL Cup was Liverpool's first reverse of the season, but while any silverware would be welcome for the as-yet trophiless Jurgen Klopp, all parties would be in agreement that the League Cup was at the bottom of their priority list.
It looked as though they might be on course for a second straight loss when the two sides quickly renewed rivalries at Stamford Bridge on Saturday, but Daniel Sturridge's stunning late equaliser ensured that Liverpool are still unbeaten in the league and sit level on points with champions Manchester City at the top.
Klopp will have no doubt taken such a scenario after seven games had he been offered it at the start of the season, and the Reds have the chance to regain their place at the summit when they host City in a mouth-watering encounter at Anfield on Sunday.
Liverpool cannot afford to let their focus drift from Wednesday's visit to Naples, though, particularly in such a competitive group. The Reds have already given themselves a headstart by beating PSG at Anfield on matchday one, and another victory at the Stadio San Paolo would be another major statement from last season's runners-up.
Klopp's side are still not at their scintillating best, though, with the front three of Mohamed Salah, Roberto Firmino and Sadio Mane in particular struggling to hit the heights of last season, when they became the most prolific Champions League trio in the competition's history.
Liverpool should have beaten both Tottenham Hotspur and PSG by a more convincing margin last month and had the chances to see off Chelsea on Saturday too. The results so far have somewhat masked the number of missed opportunities, but there is only so long a team can get away with that for.
On the bright side, if Liverpool do rediscover that killer instinct and begin blowing teams away with the type of scorelines they have threatened to do then the Reds will be a very difficult side to stop on their charge for silverware both domestically and abroad.
Napoli will not need reminding of that either, having been on the end of a 5-0 pre-season drubbing in August, with five different Liverpool players getting on the scoresheet.
Recent Champions League form: W
Recent form (all competitions): WWWWLD
The front three of Liverpool was the first thing Klopp would have put on his teamsheet throughout last season, but questions have begun to crop up recently and many of them have to do with the form of Sturridge.
The striker has scored in each of his last three appearances, including twice last week and once against PSG on matchday one.
Whether Klopp chooses to break up his usually-prolific trio remains to be seen, but the reminders being fired by Sturridge may make it easier to rest Salah, Firmino or Mane with one eye on Man City at the weekend.
There are unlikely to be wholesale changes ahead of that top-of-the-table showdown, although Naby Keita, Joel Matip, Dejan Lovren and Fabinho are among the players pushing to feature for the visitors.
Napoli possible starting lineup:
Ospina; Hysaj, Albiol, Koulibaly, Rui; Callejon, Allan, Hamsik, Zielinski; Insigne, Mertens
Liverpool possible starting lineup:
Alisson; Alexander-Arnold, Gomez, Van Dijk, Robertson; Milner, Henderson, Keita; Salah, Firmino, Mane
Head To Head
These two sides have only ever met on two previous occasions, with those coming in the group stages of the 2010-11 Europa League.
On those occasions the match in Naples ended goalless, but there was plenty of drama at Anfield as Steven Gerrard's scored a hat-trick in the final 15 minutes - including goals in the 88th and 89th minutes - to seal a come-from-behind 3-1 victory.
Liverpool have now lost just two of their last eight visits to Italian clubs, although one of those came in their most recent European away game when they were beaten by Roma in last season's semi-final.
We say: Napoli 2-2 Liverpool
Liverpool were hugely impressive away from home in the Champions League last season and are more than capable of winning in Naples as long as they begin to take more chances. Napoli are a very good side in their own right, though, and with Ancelotti in charge they also have the quality to emerge victorious, so we're sitting on the fence with a score draw.