The squad have been boosted by the return of Samuel Umtiti from injury, while Arthur misses out once again and Thomas Vermaelen has picked up another knock.
Let’s have a look at who might feature in France.
Ernesto Valverde’s biggest decision in defence concerns who will partner Gerard Pique in central defence - Clement Lenglet or Umtiti?
It’s possible Umtiti could be thrown straight in against his former club, but the sensible decision is to go with Lenglet, and Valverde likes sensible.
Elsewhere, Nelson Semedo was rested on Saturday so should feature at right-back, Jordi Alba will man the opposite flank and Marc-Andre ter Stegen will be in goal.
Sergio Busquets and Ivan Rakitic look certain starters but there’s still the question of who will replace Arthur.
It seems a straight choice between Carles Alena and Arturo Vidal, and on current form you’d have to give it to the youngster.
However, Vidal’s experience may see him get the nod ahead of the 21-year-old who has only made one appearance in the competition so far this season.
Ousmane Dembele is back to full fitness and should start this one, alongside Lionel Messi and Luis Suarez.
Barcelona were extremely wasteful in attack against Real Valladolid and will know they need to sharpen up against Lyon.
Suarez’s struggles in the Champions League have been well-documented, and he’s yet to open his account for the season. If anyone is overdue a Champions League goal, it’s the Uruguayan.
Possible XI: Ter Stegen; Semedo, Pique, Lenglet, Alba; Rakitic, Busquets, Vidal; Dembele, Messi, Suarez.
How do you think Barcelona should line up against Lyon? Let us know your thoughts, line-ups and predictions in the comments below!