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The Catalan giants play in Ukraine on Tuesday night and they currently sit top of Group G on nine points.
It has given Koeman the chance to leave key players behind and give them rest, with one of those being Messi as well as Frenkie de Jong.
"We've got various players out due to injuries and we've decided that we won't be taking Leo or Frenkie because the situation in the Champions League is quite comfortable for us with the nine points that we've got," Koeman said per Sky Sports.
"And these two players need to rest because they've played a lot of matches. So we think this is a good moment to rest them."
Barcelona are currently struggling domestically and sit 12th in La Liga, already eleven points behind Real Sociedad at the top.
Saturday saw them slide to a 1-0 defeat against Atletico Madrid thanks to Yannick Carrasco's first half effort.
Messi is yet to hit top form this season after attempting to leave the club in the summer.
Ronald Koeman, on the absence of Messi: "We have decided not to take Messi and De Jong because our situation in the Champions League is quite comfortable and they need rest. It is time to rest" #FCB :flag_ar::flag_nl::rotating_light:- Hagrid ✆ (@HagridFCB) November 23, 2020
The 33-year-old has three goals in eight games but has been attacked in the media by teammate Antoine Griezmann's uncle.
"Griezmann was convinced that he wasn't going to be successful within the first six months, but what I didn't expect was that [his struggles] would last an entire year," he said.
"Besides, with Messi, I know what's going on inside - it's not easy.
"Basically, [Messi] doesn't work hard enough at Barca and the training sessions are structured in order to please certain people, which is fine if you don't want to work.
"Antoine needs to work, even though others don't need as much effort to play well.
"He's the other way around - he needs to put in a lot of effort for himself."
Messi then hit back with: "The truth is that I'm tired of always being the problem of everything at the club."
The Argentine is yet to sign new deal at the Camp Nou and his current contract expires next summer.
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