Barca's first game back from a two-week break, in which Messi is highly unlikely to play for Argentina having missed their four matches so far this season, sees them face Atletico Madrid in a mouthwatering showdown. "He will be out for approximately three weeks", stated F.C. Barcelona on Twitter.
However, Barcelona defender Gerard Pique is optimistic that the Spanish champions and league toppers can cope without their star man, though psychologically there is a chance of them being slightly impacted by his absence. "We know what he can give to us, what it means to the opposition when Leo's on our team".
Do you think Barca will stuggle in Messi's absence?
Following Barcelona's injury update, Inter Milan said, "We regret your injury and can not face you in the next few days".
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Lopetegui, only three months into his stint with Real Madrid, defended himself against the critics.
Given Messi has been given an approximate recovery time of three weeks, there is every chance he could also miss the visit of Betis, precisely 21 days after suffering his injury and just before the next worldwide break.
The Argentine is now nearly certain to miss Wednesday's Champions League clash with Inter Milan, and will also be a huge doubt for El Clasico next weekend. Suarez buried the penalty.
Real are fifth in the La Liga standings, three points behind leaders Alaves.
"Right now that is the last thing that I'm thinking about", said Lopetegui when asked if he was anxious about losing his job.