Félix, 24, could be out for around a month, sources suggested to ESPN, with Barça due to travel to the Stadio Diego Armando Maradona in Naples on Feb. 21. The second leg is scheduled for March 12 at the Olympic Stadium in Barcelona.
Since joining on loan from Atletico Madrid in August, Félix has featured regularly for Barça this season, scoring seven goals in 28 appearances.
Barça will also be without Alejandro Balde for the rest of the season after the left-back underwent surgery on a hamstring injury.
Balde was operated on in Finland on Tuesday and will be sidelined for around four months, so he could potentially still feature for Spain at this summer's European Championships if selected.
Félix and Balde join an ever-growing list of absentees for Barça coach Xavi Hernández, who announced at the weekend he will leave the club in the summer.
The Barcelona manager also revealed centre-back Andreas Christensen has been playing with discomfort to help the team.
"We will maybe have Marc back for Granada in LaLiga [on Feb. 11]."
They then play Granada at home and Celta Vigo away before facing Napoli in their first Champions League knockout tie since 2021.