Midfielder Jack Wilshere will miss England's World Cup qualifiers against San Marino and Montenegro as well as Arsenal's Champions League match at Bayern Munich on Wednesday, Arsenal manager Arsene Wenger said.
Forward Lukas Podolski has also been ruled out of the last 16 second leg with an ankle injury.
"He (Wilshere) has an inflamed ankle, the other ankle to the one he injured before," Wenger told reporters on Tuesday before his squad left for Wednesday's last 16 second leg in Germany.
"He will be out for three weeks and will not be available against Munich, Swansea and not for England."
England play San Marino on March 22 and Montenegro four days later.
Arsenal are optimistic that Wilshere, who is currently having treatment in Dubai, will be fit to return for their Premier League match against Reading on March 30.
Wilshere damaged his left ankle during Arsenal's 2-1 defeat at arch-rivals Tottenham Hotspur in the North London derby on March 3 and has been slow to recover.
An injury to his right ankle sidelined him for the whole of last season.
Wenger added: "He has some bone bruising. The last time it deteriorated into a stress fracture. That's what we don't want to happen.
"We trust people who are specialists in this area. He was out for 17 months and we had to deal with it and so we will deal with it for two or three games."
Wenger has made several other changes to his squad as the Gunners look to overturn a 3-1 first leg defeat in London.
"Lukasz Fabianski, Abou Diaby, Andrey Arshavin and Kieran Gibbs have all been included in the 18-man group," the club said in a statement after their departure. "Wojciech Szczesny has been rested."
Arsenal will also be without defender Bacary Sagna for the match as he is suffering with knee and leg problems.
Wenger said Arsenal would have to make the "impossible possible" to stay in the competition.
"The chance is small," said Wenger, "but the chance makes the impossible possible. That would be a great credit for our team if we do it. We have to try to achieve it."