Los Che beat Barcelona in the Copa del Rey final in May but head into the game after a tumultuous week that saw manager Marcelino sacked and replaced with Albert Celades.
Barcelona will again be without Lionel Messi for the match but may be able to count on Luis Suarez after he returned to full training in the week.
Marc-Andre ter Stegen will back in action after spending the international break on the Germany bench, a situation he has openly admitted drives him pretty crazy.
Right-back Nelson Semedo could start after appearing to have recovered from an injury picked up while with the Portugal squad. However, Samuel Umtiti is back on the injured list, meaning Gerard Pique and Clement Lenglet are likely to continue at centre-back.
Jordi Alba is expected to feature at left-back, although Junior Firpo is fit again after knee trouble.
Ernesto Valverde has plenty of decisions to make in midfield and it will be interesting to see who he goes for against Valencia.
Ivan Rakitic is yet to start a game this season, Carles Alena has been left out of the last two squads entirely, and Frenkie de Jong has admitted he is yet to show his best form at Barcelona.
Arthur staked a claim for a starting spot last time out against Osasuna and could come into the line-up, while Sergi Roberto is another option in midfield.
Messi has admitted he will sit this one out and it remains to be seen if Luis Suarez will start after a few weeks out and with Borussia Dortmund up in midweek.
Antoine Griezmann should continue up front, while Carles Perez is another player who looks certain to make the starting XI.
Starlet Ansu Fati continues to train with the first team and is likely to be on the bench for this one after scoring his first Barcelona goal last time out.
Possible XI: Ter Stegen; Semedo, Pique, Lenglet, Alba; Arthur, Busquets, De Jong; Perez, Suarez, Griezmann.
How do you think Barcelona should line up against Valencia? Let us know your thoughts, predictions and line-ups in the comments below!