Messi has featured in all 11 of Barca's games to date this season, only sitting out the first 45 minutes of the game against Real Betis during the international break. In addition, he has just returned from playing two World Cup qualifiers with Argentina.
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Meanwhile, De Jong has started every Barca game since Koeman was appointed and played three times for the Netherlands last week.
Koeman said neither will travel to Ukraine for this week's Champions League fixture because he is thinking about their wellbeing -- and he urged UEFA and FIFA to do the same.
"We thought it's a good moment to give a rest to Leo and Frenkie," Koeman said in a news conference on Monday.
"Both players played all the games, mostly all the minutes, and they need to play with the national teams [last week]. Messi had a difficult trip back from South America.
"Sometimes you need to protect players because the calendar of games is incredible. It's time for UEFA and FIFA to think about what we are doing with the football players because it's crazy what they need to play."
A packed schedule has led to several injuries at Barca, with Koeman only able to name a 19-man squad for the match in Kiev, including three B team players.
Barca's only fit centre-back in the first-team squad, therefore, is Clement Lenglet. De Jong had been expected to fill in alongside the Frenchman but with the midfielder being rested, Koeman said youngster Oscar Mingueza is likely to get a chance.
It will also be a chance to see how Barca play without Messi, although Koeman insists he is still vital to the club despite the continued speculation surrounding his long-term future with his contract expiring next summer.
"We speak about Messi too much," he added. "He has always had a lot of influence in this club's success and he can still give [Barca more success]. I am convinced that he's still the player we need."
The Blaugrana travel to Kiev in a comfortable position in their Champions League group having won all three of their games so far.
However, things have been tougher domestically. Saturday's loss to Atletico Madrid was their third in eight league games this season and they have made their worst start to a top-flight campaign since 1991.
Despite that, Koeman, who was a player at the club in 1991, said he is optimistic about turning things around.
"I am not satisfied because I think we have dropped a lot of points, but I am positive about the calendar until the end of the year," he said.
"We have seven games in the league coming up and five are at home, so I am optimistic. We know the situation we're in, the decisions we have made, but my energy is focused on my job and I am happy with what the players are doing, even if I am not [happy] about the points we have."