Villa 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.
Del Bosque 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."