Messi's absence is not an issue Barcelona have often had to deal with down the years in the Champions League, particularly in recent times – the 4-0 win over Dynamo Kiev last time out was only the fourth in 43 matches in the competition that he has not featured in.
Nevertheless, one would expect Barca to have enough firepower to see off their hosts, Ferencvaros, on Wednesday and they are undefeated in their previous nine Champions League games without Messi since a 2-1 loss to Ajax in November 2013.
Barca crushed the Hungarian champions 5-1 at Camp Nou in October and are already assured of a place in the next round having won all of their first four matches in Group G.
As such, Koeman wants to take every opportunity to rest his star man in what is proving a hectic season.
"I understand that it is not normal, but in the calendar this season there were two moments for Leo Messi to rest, Kiev and tomorrow, because we are already qualified," Koeman told reporters on Tuesday.
"It allows me to give opportunities to other players and the Saturday games in the league are very important. From tomorrow there is no more [chance] to rest him.
"Leo is always Leo. He is very important in our attack. When the ball reaches him, it may be that at the beginning of the season it has cost him a little [in terms of fatigue]. He may not score 30 goals per season, but he is working well and it is very important in our attack.
"He always likes to play and it's good that he has this mentality, but I spoke with him and asked him, but the final decision is up to the coach.
"I wanted to give him rest in Kiev and tomorrow. For the rest of the season he may not get any more rest because we play every three days."
Marc-Andre ter Stegen and Philippe Coutinho are two others who have been afforded a rest and left out of the travelling party.
Messi is expected to return for Barca's final group match next week against Juventus and long-time rival Cristiano Ronaldo.