The Argentine icon has already scored 12 goals and made five assists for the La Liga giants this season, but he will now endure a stint on the sidelines.
Why is Lionel Messi not playing against Inter Milan?
The five-time Ballon d'Or winner lasted just 23 minutes of Barcelona's 4-2 win over Sevilla before leaving the pitch injured.
It has since been revealed that he has been ruled out for three weeks with a broken arm.
And the 31-year-old was snapped wearing a sling for the first time on Tuesday.
Ernesto Valverde's side are top of Group B following a 4-0 win over PSV Eindhoven and a 4-2 victory Tottenham.
What has Ernesto Valverde said about Lionel Messi's absence?
The Barca boss said: "Clearly his absence will affect us.
"But it'll also be a challenge for us, to see if we can win even without him in the next few weeks where we have some really tough games.
"We could change our system, but not our style.
"We have various options but I don't give want to give the Inter coach any hints.
"One player can't replace Leo, it'll be a collective responsibility.
"The doctors have spoken about three weeks but we hope we can reduce that time.
"It's not a muscular problem though, so I don't think it can be reduced that much."
Will Lionel Messi be fit for El Clasico?
Barcelona will take on Real Madrid at the Nou Camp on October 28.
The Argentina international will not be fit to face Julen Lopetegui's side.
If he is out of action for three weeks, he will return before the La Liga clash against Real Betis.
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