Bookies Bodog say they are very keen to remain at the industry top price of 11/4 about Spain winning Euro 2012 this summer.
The firm believe the failure of either Real Madrid or Barcelona to reach the Champions League final, coupled with question marks over the nation's striking options, makes them vulnerable favourites.
"The loss of striker David Villa is a very big blow to Spain's hopes of winning this tournament because you only have to look at how influential he was in the successful World Cup campaign of 2010 and the European Championships of 2008.
"Barcelona would probably have hammered Chelsea with a fit Villa up front in the recent Champions League semi," said Nick Gray of Bodog.
Villa has scored 51 goals in 82 national team appearances for Spain.