Liverpool's medical team are working to get the 25-year-old ready for the trip to Goodison Park and the return leg against City next week but Klopp said he would not take any chances.
"I can't make Mo available because it's the derby, I'd never do it. It's not possible. I don't think any of our supporters want us to do that," Klopp told a news conference on Friday.
"I don't think it makes sense to talk here about what we do with the boys in rehab. But, of course, you can imagine we have tried everything to make him available.
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"If he's a doubt, he'll not be involved. That's how it is with all of them. I would not rest a player with absolutely nothing, with no problem."
Salah, who has 38 goals for Liverpool in all competitions this season, could be replaced by fit-again forward Danny Ings, who is looking to make his first start under Klopp.
The 25-year-old has endured long spells on the sidelines with two knee injuries since the German manager took over at Anfield in 2015.
Liverpool are third in the table with 66 points from 32 games and a win against ninth-placed Everton will take them a point above Manchester United.
United face neighbours Manchester City later on Saturday.
"The derby is the most important game for the people so that is how we take it. We do the job, people have the dreams. In this special game we have to show up. You have to deliver."
(Reporting by Shrivathsa Sridhar in Bengaluru; Editing by Toby Davis)
