Dominik Szoboszlai was a star for Salzburg during their Champions League group stage but left to join RB Leipzig in January.
Salzburg will be without first-choice centre-back pairing for the first leg with Andre Ramalho suspended and Maximillian Wober injured.
Brenden Aaronson has featured regularly for Salzburg since his arrival from MLS side Philadelphia Union in January but may only make his European debut from the bench.
Manu Trigueros is fresh to return after missing the 2-1 defeat to Real Betis over the weekend through suspension.
Villarreal were so short in midfield at the weekend that Tottenham loanee Juan Foyth, who is a defender, had to play there against Betis.
The Spanish side could be missing five players when they face Salzburg on Thursday, but Etienne Capoue was back on the bench against Betis after missing their last three games.
Gerard Moreno barely featured in the group stage but may be required here due to their injury problems.
Salzburg have dropped down from the Champions League group stage and will be fancied to go deep in the Europa League. However, they lost star attacker Dominik Szoboszlai in January and head into Thursday's clash with Villarreal without their first-choice centre-back pairing.
Villarreal's form has tailed off at the worst possible moment. The Spanish side have lost two of their last three matches, as many defeats as their previous 31 matches combined in all competitions this season. They have only won two of their last eight and both were in the cup to lower league opposition.
While form would suggest Villarreal will suffer on Thursday, in Unai Emery they have a head coach that loves the Europa League. For that reason you cannot count against the Yellow Submarines not only coming through this tie but going deep in the competition.
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