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Alex Oxlade-Chamberlain will miss next month's European Championships after being ruled out for up to two months with a knee injury.
Oxlade-Chamberlain initially sustained the injury when he collided with Barcelona's Javier Mascherano during the first-half of Arsenal's 2-0 Champions League defeat in February.
Following scans it was revealed that the midfielder would be available within six to eight weeks and had returned to training on April 23.
However, he has suffered a fresh knee injury in training on Monday and is set for an extended spell on the sidelines which will end his hopes of being included in England's squad for Euro 2016.
"We lost Oxlade-Chamberlain, and he will be out for six to eight weeks I think. It's very sad. He was physically ready and sharp in training," manager Arsene Wenger told a news conference on Friday.
"There is no chance of the Euros for him. He will be back at the beginning of July."
Centre-back Per mertesacker will also miss the rest of the season due to a hamstring problem, but Santi Cazorla could feature against Manchester City on Sunday after playing for the club's Under-21s during the week.
"Cazorla came through an Under-21s' game well. The season is over for Mertesacker due to his hamstring," Wenger said.
Meanwhile, the manager has revealed that Mikel Arteta will leave the club when his contract expires at the end of the season.
Arteta joined Arsenal from Everton in 2011 and was appointed club captain in August 2014 following Thomas Vermaelen's departure.
The Spaniard made 148 appearances in all competitions, scoring 16 goals, but he has not started a single Premier League game this season due to injury and dropping out of Wenger's plans.
Wenger has confirmed that he will leave Arsenal and could join Pep Guardiola's coaching team at Manchester City.
"It is true that he is out of contract here and his contract finishes. It is a good opportunity for me to thank him for his contribution, not only as a player but also as a leader," Wenger said.
"I heard about that possibility (City). He is able to inform you much better than I. He is free to decide what he wants.
"I still think he can play and in the last months he has come back to a very good physical level. He is in a position today to continue to play. He would still be a very good player.”