Real Zaragoza frontman Postiga has been ruled out with a thigh injury, meaning coach Paulo Bento will be unable to field the same starting line-up which he has used in the last six competitive matches.
Besiktas forward Hugo Almeida is expected to get the nod in Donetsk, with 20-year-old Nelson Oliveira, who has come on as a substitute three times in the tournament, likely to be on the bench again.
Almeida, who was sat alongside Bento at Tuesday's pre-match press briefing, said: "I'm very satisfied with that.
"I've worked a lot to be called to the starting line-up and I'll take this opportunity. I want to show my very best, that's logical. I've always been motivated, like all 23 players in the squad. We were the ones chosen and all of us want to play.
"Of course, I was a little sad not to be in starting lineup, but it's all about work. When your opportunity comes, you have to be at your very best to help your team on the pitch," he added on Uefa.com.
Spain coach Vicente del Bosque reported no new injury problems following the quarter-final victory against France.
However, he must decide whether to start the game again without a recognised striker and allow Cesc Fabregas to fill the role.
If Del Bosque decides against the quarter-final line-up, Fernando Torres could lead the line, while Pedro could also get a start in the Spain midfield.