Spain manager Vicente Del Bosque admits the absence of David Villa strikes a blow after he failed to recover from his broken fibia in time for Euro 2012.
The Barcelona striker is the national side's all-time leading scorer with 51 goals in 82 games but has not played since December and finally ruled himself out of contention this week despite a desperate late attempt to be fit in time for the naming of Del Bosque's squad on Sunday.
The former Real Madrid boss told AS: "We had experience with this type of injury but we didn't want to hamper his efforts.
"Everyone was telling us he was doing very well in his physical preparation and everything would be fine for the national team so this has been a setback.
"There were also those who said he wasn't going to arrive, but I knew he was very special.
"He has been vital in winning the Euros and the World Cup so it isn't strange that we were hoping we would make it."
Despite losing their talisman, Spain are still favourites amongst many to retain the title they won in Austria four years ago and Del Bosque does not believe that expectation is a negative thing for the squad.
He said: "Before the World Cup and now there has been optimism and that is healthy. They are putting us as favourites and we can't hide that. This is the reality but we know there are very strong countries and we have to fight like sportsmen."
The final squad of 23 will not be named until Sunday due to Barcelona and Athletic Bilbao's participation in the Copa del Rey final on Friday night.
Spain begin their preparations for the Euros with a friendly against Serbia on Saturday and, although Del Bosque has been working with a rather different squad this week to the one that will eventually go to Poland, he still believes the experience has been a fruitful one.
"When you make a squad or a line-up you always hurt someone because you can't play everyone so imagine how it must feel to not go to the European Championships," he said.
"In the training sessions it has been as if everyone was going to continue.
"They are a high-quality squad and you can only pick 23, but they have to use this feeling as an incentive for the future. Some of them had already gone on holiday but have come here and been brilliant, I can't have a single complaint."