Following a fascinating 1-1 draw in Italy last month, both clubs have remained unbeaten, but a series of injuries may now threaten Barca's hopes of going through.
Here, Sports Mole rounds up the latest team news ahead of a mouthwatering clash at Montjuic.
BARCELONA vs. NAPOLI
BARCELONA
Out: Frenkie de Jong (ankle), Pedri (thigh), Gavi (knee), Alejandro Balde (hamstring), Marcos Alonso (back)
Doubtful: Ferran Torres (thigh), Raphinha (ankle)
Sports Mole's predicted XI: Ter Stegen; Kounde, Araujo, Martinez, Cancelo; Gundogan, Christensen, Lopez; Yamal, Lewandowski, Felix
NAPOLI
Out: Jens Cajuste (thigh), Cyril Ngonge (muscular), Piotr Zielinski (ineligible), Leander Dendoncker (ineligible)
Doubtful: Amir Rrahmani (adductor)
Sports Mole's predicted XI: Meret; Di Lorenzo, Ostigard, Jesus, Olivera; Anguissa, Lobotka, Traore; Politano, Osimhen, Kvaratskhelia
For data analysis of the most likely results, scorelines and more for this match please click here.