Ronald Koeman's side are searching for a first win in four games and has decided to try without their greatest ever player.
Messi has scored one goal in six LaLiga games, but three in the Champions League, including in the recent 2-1 win against Dynamo Kiev.
An out of context clip of the Messi deep into stoppage time apparently walking around looking disinterested was widely shared on social media during that game, but Koeman said nothing could be further from the truth.
"Messi is mentally good, enjoying this sport. He's a winner and sometimes you go through moments when the ball doesn't go in, but he looks really focused on that subject.
"I think Messi still has so many qualities. He's very important in our game. He scored the penalty and we're used to him making the difference here, and he's still a very decisive player."
#Culers! Here's your starting XI for #BarçaBetis!