After 22 minutes at the Estadio Benito Villamarin, Lionel Messi hobbled off the pitch with a thigh ailment.
It's the latest setback of a troublesome season for the Argentine, who has sustained three separate injuries so far and appears subdued as a result.
Gerardo Martino has coaxed the former Arsenal man into world-class form from central midfield, and while he's never entirely convinced as a false nine for Barca or Spain, he's the right choice in that role while Messi is out even with Alexis Sanchez and Neymar on the roster.
Alexis is Barca's second top scorer so far this season with seven goals from 10 starts, per WhoScored.com, but he's doing his damage in the right-forward role.
It's the position he excelled in at Udinese before his big move, and Martino's more direct, vertical system has allowed the Chilean to express his natural athleticism and engine.
Coming in off the edge, he's lethal, with the speed of an Olympian and the finishing ability of a naturalised striker. La Blaugrana have a multitude of players who can craft him three or four chances per game in this position, but that number drops when he becomes centralised.
It's no knock on Alexis' ability, more an honest truth, in saying that he's not at the "Barca level" in possession and in tight spaces. The false-nine role is extremely specific, and it doesn't play to his strengths.
At national level, Jorge Sampaoli plays Alexis from the right with Jorge Valdivia (as a No. 10) the furthest forward central man. Recent results have been superb.
They could ditch the role and play with a true No. 9—and let's be honest, Messi is getting closer and closer to that with every passing month—but why ruin a good thing? This template has them unbeaten after 13 La Liga games.
Neymar is the other choice, and while his return of four goals and seven assists in nine starts is superb, he's perfecting his craft as one of the finest left forwards in the game and wasn't bought to replace Messi, more play alongside him.
He's played the central role twice this season, but has his acclimation been so quick that he's able to take the reins in what is arguably the most important position in the side?
It's not worth the risk, and the prospect becomes even less appealing when you consider the presence of Cesc in the side—a man who's played the role more than 20 times.
Cesc has been excelling as a central midfielder, and while a block of games in that role could see him become the form midfielder in Europe, he's the logical choice for the centre-forward role. He links play better than the other two, feels more comfortable in central areas and has better chemistry with his deeper midfielders.
Messi could be rested for a significant chunk of time as Barca seek to protect their prized asset, and "Tata" must make a decision. The squad is deep and full of options, but there's only one choice.