Coach Christophe Galtier said on Thursday that Messi, who lifted the World Cup on December 18 at Lusail stadium in Qatar, took part in training over the last couple of days.
But he felt the South American great needed a bit more time to be ready to play competitively.
"He's had a fantastic World Cup. He had commitments, going back to his country for the celebrations and we wanted him to recover back home with his family," Galtier said ahead of Friday's trip to Chateauroux in the round of 64.
"He will not play tomorrow. Having discussed with him, we want him to be ready for the following game (against Angers in Ligue 1)."
Ligue 1 leaders PSG, who suffered their first competitive loss this season when they were beaten 3-1 at second-placed RC Lens last Sunday, will be without their star attacking trio.
France forward Kylian Mbappe, who was on the losing side in the World Cup final despite scoring a hat-trick, has been given a break and travelled to New York with friend and teammate Achraf Hakimi while Brazilian Neymar skipped training on Thursday.
"We knew there would be absences after the World Cup. As for Neymar's absence in training, it had been scheduled after all players were assessed upon their return from the World Cup," said Galtier.
"We decided with the medical staff that Neymar, with everything he has experienced with his ankle problem in Qatar, needed time. He won't play tomorrow."
Galtier, however, insisted he would field a "very competitive team", with Costa Rica keeper Keylor Navas being handed a start in place of Gianluigi Donnarumma as PSG look to put their RC Lens loss behind them.
