Ousmane Dembele is fit and ready to make his debut, Luis Suarez is also fit again after featuring for Uruguay during the international break while Ivan Rakitic is a doubt.
Let’s have a look and check out who could be given the nod on Saturday.
Defence – Semedo to start?
In goal Marc-Andre ter Stegen will start, but it’s ahead of him where Valverde has his first decision to make, at right-back. Should he go for Aleix Vidal, who started last time out in the 2-0 win over Alaves, or should he go back to summer signing Nelson Semedo?
It’s difficult to see where he will go with this one, but Semedo impressed against Real Betis and surely deserves the chance to press his claim to be the club’s undisputed first choice at right-back.
In central defence Gerard Pique should partner Samuel Umtiti while Jordi Alba, back in form and favour, should start at left-back.
Midfield – A full debut for Paulinho?
Into midfield and there are more dilemmas for Valverde. Rakitic picked up an injury while on international duty, and although he was pictured in training, it’s unclear if he is fully fit, and Valverde may not want to take any risks with him.
Andres Iniesta may also miss out, the 33-year-old featured for Spain in midweek, and could be given a breather, particularly with Juventus up next in the Champions League in midweek.
Should Valverde go without the pair it’s possible he could hand Paulinho a full debut. The summer signing has been much maligned but was on target yet against for Brazil during the international break, in a 2-0 win over Ecuador.
Elsewhere Sergi Roberto should also get the nod, the midfielder has impressed in the opening two Liga games and deserves to keep his place, with Sergi Busquets completing the midfield.
Attack – Dembele to debut?
Into attack and we should hopefully see the new Barcelona frontline of Lionel Messi, Luis Suarez and Ousmane Dembele.
Messi has been the difference for Barcelona in the first two games of the season, although he’s not looked entirely happy, and you can expect his body language to be scrutinised even further on Saturday.
Suarez should also make his first Liga start of the season after recovering from injury, with Paco Alcacer making way.
And on the left we will hopefully see Dembele, who should go straight into the side at the expense of Gerard Deulofeu.
Deulofeu has done a decent job since returning to the club, but Dembele brings a real buzz.
Can he join the likes of Johan Cruyfff, Romario, Rivaldo and Ronaldinho in scoring on his Camp Nou debut?
Predicted line-up: Ter Stegen; Semedo, Pique, Umtiti, Alba; Busquets, Paulinho, Roberto; Messi, Suarez, Dembele.
Who do you think should start against Espanyol? Let us know your thoughts and line-ups in the comments below!