Messi, who made his PSG debut at Reims before the international break, and Neymar both played as late as Friday (AEST) in respective FIFA World Cup qualifiers for Argentina and Brazil.
While Neymar scored and provided an assist in Brazil's 2-0 win over Peru, Messi netted a hat-trick against Bolivia, surpassing Pele as the all-time leading goalscorer for a South American nation in the process. Argentina subsequently celebrated its recent Copa America triumph with fans finally allowed back into the stadium in Buenos Aires.
Angel Di Maria and Leandro Paredes also featured for Argentina and Pochettino said a common-sense approach dictated none of the players would be involved in Sunday's (AEST) home match against newly promoted Clermont.
"Di Maria, Paredes, Neymar and Messi, due to common sense, they are not going to be involved in the squad tomorrow," Pochettino said, though PSG's coach is hoping to have Mauro Icardi, Presnel Kimpembe and Mbappe, who suffered a calf injury while on France duty, will be fit to feature.
Mbappe was at the centre of one of the biggest stories of the recently closed transfer window, with PSG rejecting three bids from Real Madrid for its star striker.
The 22-year-old only has a year left to run on his contract and reports have suggested Madrid is confident he will sign for the Spanish giant as a free agent in 2022. For now, though, he remains at PSG, where Pochettino insists he is content.
"Mbappe is happy. He is emotionally stable. Before the end of the transfer window and now, he has stayed in the same positive mindset with the desire to play and enjoy himself," he said.
"So we are happy with how he is feeling. He has been training and recovering from the injury that he picked up on international duty. We hope he can be available tomorrow."
While PSG has incredible star power in attack, Pochettino has been keen to point out there is a balance to be struck. Indeed, his side conceded five goals across its opening three Ligue 1 fixtures and though it sits pretty on 12 points from four matches, the former Tottenham Hotspur boss knows there is work to do.
"I think all the players at PSG are stars. Some might play more or less, but they are all stars," Pochettino, who is also set to be shorn of Marco Verratti on Sunday (AEST), said.
"PSG as a club is bigger than any individual. We have a squad of around 35 players, they all need to feel important. In terms of managing the squad, which is our job, we need the tools so that the 35 players can feel at home and accept their place but at the same time, there are some fantastic names.
"We have to make sure they work as a team because this is a team sport and that is a big challenge that we face. I have been saying that since the start, so we are going to work hard so that it is not just about the names of Kylian, Neymar or Messi, but so that everyone feels comfortable.
"They all need a team, a structure and an organisation to win games so that has to be our main thought. We all drive towards that."
Two of PSG's latest arrivals are yet to make their debuts. UEFA Euro 2020 winner Gianluigi Donnarumma has been on the bench for the past two games, while Sergio Ramos is still working his way back to fitness.
Asked if Donnarumma could make his bow against Clermont, Pochettino replied: "We haven't decided yet who is going to be in goal. We have different options – Donnarumma is one of those options."
Pochettino also confirmed Sunday's (AEST) game, as well as next week's UEFA Champions League meeting with Club Brugge, would come too soon for former Madrid captain Ramos.
"Ramos is still undergoing recovery and will not be available for that match," he explained.
"He is following the steps. We want all the players to be available as quickly as possible but it is not something that worries me. I am sure Sergio will recover well and be available soon."