Alejandro Balde and Sergi Roberto are also doubts with a back injury and gastroenteritis respectively, but reports have claimed that Pedri could make a rapid return from a thigh problem in time to feature, and Roberto is also in the squad.
Koeman will also welcome back Frenkie de Jong from a domestic suspension and could therefore have his first-choice midfield available with Sergio Busquets raring to go, meaning that youngsters Gavi and Nico Gonzalez are set to be demoted.
Oscar Mingueza and Sergino Dest seem set to occupy the full-back areas while Roberto, Balde and Alba remain uncertain, while one defensive change could see Ronald Araujo introduced in place of Eric Garcia.
Ansu Fati took all of 10 minutes to mark his return to action with a goal against Levante, but Koeman may be reluctant to start the 18-year-old on Wednesday after such a lengthy layoff.
As a result, an unchanged front three should see Philippe Coutinho, Luuk de Jong and Memphis Depay all start at the Estadio da Luz, with the latter netting in back-to-back games for Lyon against Benfica in the 2019-20 tournament.
Barcelona possible starting lineup: Ter Stegen; Mingueza, Pique, Araujo, Dest; F. de Jong, Busquets, Pedri; Coutinho, L. de Jong, Depay