"We are very excited to still be around in this tournament but it has been tiring," U.S. captain Landon Donovan said at a news conference in Bloemfontein on Tuesday.
"It's a big challenge in a lot of ways. It's a game in which we know they will have a lot of possession and a big part of playing against them is not getting frustrated.
"On the other hand, we need to try and put them under pressure and see how they react to that," added the 27-year-old.
"We have never been to the semi-final of a tournament of this calibre and in some ways this is even tougher that the World Cup just in terms of the quality of opposition."
In terms of quality, it does not get any better than Spain, the European champions who extended their winning run to a record 15 matches with three comfortable victories in the group phase.
The U.S. lost their two opening group games to Italy and Brazil but staged a near-miraculous recovery to beat Egypt 3-0 in their last Group B game in Sunday and qualify for the last four ahead of the world champions on the number of goals scored.
"It's a big accomplishment to have gotten to this point," Donovan added.
U.S. coach Bob Bradley said he expected Spain to pose myriad problems for his team.
"They play the ball quickly, the keep possession well and they have some special players," Bradley said. "But we have the ability to put their defence under pressure. It will take a good game plan and a complete effort from the players to beat them."
Bradley said goalkeeper Tim Howard would return to the starting line-up after Brad Guzan was given a chance to play against Egypt. Defender Carlos Bocanegra is still not sure of a place despite returning to training after a hamstring injury.
The winners advance to the final in Johannesburg on Sunday where they meet either Brazil or hosts South Africa whose semi-final is at Ellis Park on Thursday. The third place playoff match is on Sunday in Rustenburg.
