The decision was taken to hand the 33-year-old a well-earned rest as positive progress was already being made through continental competition.
Barca had no need for Messi magic against Ukrainian opposition and will be hoping to see history repeat itself on Wednesday.
Koeman’s side will be heading for Budapest 24 hours before facing Hungarian foes on a European stage.
They have enjoyed a faultless run through their Group G campaign so far, with maximum points taken from four fixtures to date.
A place in the last-16 is already secured, which means that Koeman finds himself in the enviable position of being able to shuffle his pack through two more contests.
Messi will be rested again for the first of those, with the intention being to keep him fresh for bigger challenges to come.
Koeman has said: "Considering this season’s schedule, there are only two moments where Messi can rest, in Kyiv, and tomorrow. From tomorrow, there will be no more opportunities. Qualifying already also influences the decision."
Rotation within Barca’s ranks also means that Marc-Andre ter Stegen will be handed a break between the sticks.
Philippe Coutinho is another senior star set to remain in Catalunya as his team-mates go in search of another morale-boosting success.
Frenkie de Jong was given a Champions League week off alongside Messi against Dynamo Kiev, but he does form part of the travelling party this time.
Clement Lenglet is also included in Koeman’s squad despite nursing a slight knock.
The French defender picked up an ankle complaint against Osasuna over the weekend to cast doubt over his involvement against Ferencvaros.
It may be that no risks are taken on him in midweek, with the option there for the 25-year-old to be saved for a La Liga clash with Cadiz on Saturday.
Barca are, however, already without the services of Samuel Umtiti and Gerard Pique at centre-half, with it suggested that Koeman will look to dip into the January transfer market for another defensive option.
For now, though, his focus is locked on the present and guiding his side to three points without Messi – who did not take part in training on Tuesday as plans for a meeting with Ferencvaros were finalised.