The former Man City winger, now a flying full-back, hurt his hip against Eibar and has missed the last four matches, with a comeback for European action looking very unlikely.
The Spanish side are also missing Lucas Ocampos with an ankle sprain and Marcos Acuna with a ruptured thigh muscle.
There are more positive news over the possible involvements of Sergi Escudero and Oscar Rodriguez, though.
Both players made the bench in the weekend win over Huesca, and could be in contention to feature against Dortmund.
Jules Kounde could return to the starting XI alongside Diego Carlos after being rested at the weekend, with Aleix Vidal continuing to deputise for Navas at right-back.
Head coach Julen Lopetegui will have to choose between Nemanja Gudelj and Joan Jordan to partner Ivan Rakitic in the centre of the midfielder.
Munir scored the winning goal against Huesca so could be preferred to Suso on the right of the attacking midfield trio, with new signing Alejandro Gomez and Oliver Torres in behind the striker, too.
Luuk de Jong and Youssef En-Nesyri are competing for the centre-forward spot, and the latter will likely be given the nod.
Dortmund, meanwhile, are missing a plethora of starts for the first leg.
Roman Burki, Marcel Schmelzer, Lukasz Piszczek, Dan-Axel Zagadou, Axel Witsel, and Thorgan Hazard will all miss out.
Thomas Meunier has recovered from injury and could play a part, though likely not from the start.
The Bundesliga side might be without Thomas Delaney too as his wife is about to give birth, but he has been registered and could make the squad depending on his family matters.
Emre Can will continue at right-back in a back four alongside Mats Hummels, Manuel Akanji, and Raphael Guerreiro.
Should Delaney be unable to play, Mahmoud Dahoud should step into central midfield with Jude Bellingham.
Jadon Sancho and Erling Haaland are sure fire starters, with Marco Reus perhaps coming in to replace Gio Reyna.