It’s a tricky game for Ernesto Valverde’s side after a goalless first leg as they look to book their place in the quarter-finals of the competition.
Let’s have a look at who might feature:
There are a couple of big questions in defence for Valverde for this one at centre-back and right-back.
The Barca boss must decide between the fit-again Samuel Umtiti and Clement Lenglet in central defence, while it’s between Sergi Roberto and Nelson Semedo on the right.
The rest of the defence will be completed by Gerard Pique and Jordi Alba, with Marc-Andre ter Stegen in goal.
It’s vital Barca defend well against Lyon and prevent them from grabbing an away goal that would make the hosts’ task even tougher.
It looks likely that Valverde will go with his favoured midfield three of Sergio Busquets, Ivan Rakitic and Arthur against Lyon as the trio are all fit and available.
Rakitic should be pretty fresh after only playing 10 minutes on Saturday, while Arthur only featured in the first half.
Arturo Vidal may also be in the reckoning after a fine display against Rayo Vallecano at the weekend, while Carles Alena is another possible option.
Ousmane Dembele is expected to miss out against Lyon after picking up a hamstring problem on Saturday which is a big blow for Barca.
Luis Suarez and Lionel Messi will both start in attack, but the question is who will play alongside the duo in Dembele’s absence?
Philippe Coutinho will be hoping that he is the man chosen but given his poor form there’s no guarantee the Brazilian will come into the team.
Malcom is another option, although he is yet to start in the Champions League for Barcelona, while Roberto could also play further forward with Semedo in defence.
Possible XI: Ter Stegen; Roberto, Pique, Umtiti, Alba; Rakitic, Busquets, Arthur; Messi, Suarez, Coutinho.
How do you think Barcelona should line up against Lyon? Let us know your thoughts, predictions and line-ups in the comments below!