The reigning Serie A champions visit last season's La Liga winners at their temporary home of Montjuic, having played out a 1-1 home draw late last month.
Robert Lewandowski's goal in Naples maintained Barca's unbeaten record against their Italian counterparts, who must now produce a first win over the Blaugrana to prevail over the course of two legs.
Here, Sports Mole takes an in-depth look at the head-to-head record and previous meetings between the two sides.
Head-to-head record
Previous meetings: 7
Barcelona wins: 4
Draws: 3
Napoli wins: 0
Though the 'Maradona derby' was a rarely-played fixture until relatively recently, Barcelona and Napoli have been drawn together several times in UEFA competition over the past few years, with both finding the net on each occasion.
Having relied on returning hero Victor Osimhen to rescue a first-leg draw in February's encounter at Stadio Maradona - following Robert Lewandowski's trademark opener - the Serie A side are still to get the better of their Spanish counterparts after seven attempts.
They also held the Blaugrana to a 1-1 draw on their most recent visit to Catalonia, back in February 2022, but were beaten one week later on home turf, as the teams met in the Europa League's knockout phase.
Goals from Jordi Alba and Frenkie de Jong put Barca in control, and though Napoli halved their deficit soon after - thanks to a Lorenzo Insigne penalty - the visitors struck twice more, through Gerard Pique and Pierre-Emerick Aubameyang; Matteo Politano's late strike was therefore no consolation for fans of the Partenopei.
A couple of years earlier, the clubs had clashed in the Champions League's last 16, with their two-legged tie played either side of a six-month hiatus amid the COVID-19 pandemic.
In February 2020, goals from Dries Mertens and Antoine Griezmann saw the spoils shared in Naples, but nearly half a year later, at an almost empty Camp Nou, Barcelona strode through to the quarter-finals with a 3-1 second-leg triumph.
Booking a contest with eventual winners Bayern Munich, Clement Lenglet, Lionel Messi and Luis Suarez all scored before the break, with the latter coolly converting a penalty won by his good friend Messi.
There was still time for Insigne to respond from the spot, at the end of an action-packed first half, but Napoli could not close the gap further and Barcelona ran out 4-2 winners on aggregate.
Just ahead of that ill-fated 2019-20 season, Messi was ruled out of Barca's U.S. tour with a calf injury, but that did not stop his teammates winning both high-profile friendlies, hosted in Florida and Michigan respectively.
Previous meetings
Feb 21, 2024: Napoli 1-1 Barcelona (Champions League Round of 16)
Feb 24, 2022: Napoli 2-4 Barcelona (Europa League Qualifying Playoffs)
Feb 17, 2022: Barcelona 1-1 Napoli (Europa League Qualifying Playoffs)
Aug 08, 2020: Barcelona 3-1 Napoli (Champions League Round of 16)
Feb 25, 2020: Napoli 1-1 Barcelona (Champions League Round of 16)
Aug 10, 2019: Barcelona 4-0 Napoli (friendly)
Aug 07, 2019: Napoli 1-2 Barcelona (friendly)
Champions League meetings
Feb 21, 2024: Napoli 1-1 Barcelona (Champions League Round of 16)
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