Koeman said the defensive pair could also miss Sunday's league visit of Burnley.
"Keane and Jagielka are out for tomorrow and doubtful for Sunday. Rest is the same list. (A) total (of) seven players are unavailable for tomorrow," Koeman told a news conference on Wednesday.
Another notable absentee is in-form striker Oumar Niasse who was not registered by Everton for the group stage at the start of the season. The 27-year-old Senegalese has burst onto the scene with three goals in his last two matches.
News that makes sense
Your trusted source for staying up-to-date with the world around you. Get free daily news updates and analysis, straight to your inbox.
"We had to make that decision already a long time ago. At that time his situation was different from the situation now. In life you don't get a second chance," Koeman added.
"That decision was made by players not available. In a few weeks some of those players can be available again and we will see."
Following four straight defeats to Chelsea, Tottenham Hotspur, Atalanta and Manchester United, Everton appear to have turned a corner with consecutive wins at Goodison Park.
Koeman reckons the team's confidence is recovering and they will only improve with home games against Limassol and Burnley over the next four days.
"I think the wins in the last two games against Sunderland and Bournemouth is important," said the Dutch manager.
"It is really important to play full of confidence. They (the players) get it by themselves and through good results. We need to play better, more aggressive, we play at home and we need to win."
Limassol collected a point from a 1-1 draw at home to Olympique Lyonnais in their Europa League Group E opener, while Everton suffered a 3-0 defeat at Italian side Atalanta.
(Reporting by Hardik Vyas in Bengaluru; Editing by Ken Ferris)
