Foot surgery will leave the Spain international sidelined for four months.
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Merino has not played since Arsenal's 3-2 loss against Manchester United on January 25 and is set to undergo surgery on his foot on Monday.
“It’s a big blow," Arsenal manager Mikel Arteta said yesterday.
"Mikel offers something unique in the team but he’s going to be out for four months unfortunately with a very rare injury, so we need to support him, make sure that he’s very connected with the team because he can still add a lot of value to the players and the staff and keep him around.”
The extended period also puts Merino's place in Spain's World Cup squad now in jeopardy.