According to the Associated Press, Puyol underwent arthroscopic knee surgery in May after experiencing pain in his knee after a Barcelona victory against Espanyol.
He is having the right knee operated on, one year after having work done on his left in 2011.
Without Puyol in the back line as a stopper, Spain loses one of their more vocal leaders. His experience at the position as well as being one of the best defenders in soccer today would have really helped Spain in their title defense.
Puyol is also a strong player in the box, physically asserting himself on corner kicks as he boxes out strikers and clears any potential threats.
Not only that, Puyol has been known to score on occasion during corner kicks, just like he did two years ago in the World Cup semifinals against Germany.
Villa's absence will definitely make it harder for Spain to defend their title also. Villa broke a shin bone in December, and the recovery timetable is between three and six months, conflicting with Euro 2012.
Villa played a big part in Spain's World Cup championship; he was the tournament's Silver Boot winner and is a dynamic player at the striker position.
As quoted in the New York Daily News, Spanish coach Vicente Del Bosque is saddened at the loss of his two star players but is sure that their replacements will be more than adequate during the tournament.
"These two injuries are important setbacks to us," Del Bosque said. "But I think the players who will come in for them are also of high quality."
Iker Muniain, Pedro Rodriguez and Adrian Lopez are the three players who are vying for Villa's position for the tournament.
Without these key players, Spain may find themselves in trouble once they play the other pre-tournament favorite, Germany.
Germany is in Group B while Spain is in Group C. Depending on the order of qualification, Spain might play Germany in the semifinals.
If so, Germany might knockout Spain, retribution for their losses to the Spanish squad in the 2010 World Cup and the previous European Championship.
If Spain wants to win Euro 2012 and become one of the best teams in FIFA history, they need to patch up their center-back and striker positions. The losses of Villa and Puyol might prove too insurmountable for Spain.