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Vicente Del Bosque admits the news Carles Puyol is set to miss Euro 2012 with a knee injury is a major blow for defending champions Spain.
Barcelona announced earlier on Monday Puyol will undergo an arthroscopy on May 12 after feeling discomfort in his right knee after Saturday's 4-0 defeat of Espanyol with the approximate recuperation period around six weeks.
That means the 34-year-old is definitely out of Barca's final Primera Division game at Real Betis at the weekend and he will also miss coach Pep Guardiola's last game in charge - the Copa del Rey final against Athletic Bilbao on May 25.
His participation at Euro 2012 is also extremely doubtful with the world and European champions opening their campaign against Italy on June 10 before going on to play the Republic of Ireland and Croatia in Group C.
Del Bosque told AS: "It's a serious setback, he's a considerable loss not only for what he gives on the pitch, but for what he contributes to the team (off it)."
Puyol has won 99 caps since making his international debut in 2000 and was part of the Spain squad that won Euro 2008 and the 2010 World Cup.
Del Bosque added: "It's also a shame that this happened when he was on the verge of playing 100 caps, but hopefully he can get there. He was having a great end to the season."
The Spain coach is also waiting on the fitness of Puyol's Barcelona team-mate David Villa, who has been sidelined since Christmas with a broken leg.
Del Bosque will announce his provisional squad for the competition on May 15 which will then be whittled down when the final 23-man party is confirmed on May 27.