Messi had a puzzled look on his face as he walked past PSG head coach Pochettino, having been replaced by full-back Achraf Hakimi in the 76th minute of the league clash.
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Pochettino and Messi briefly exchanged words before the latter, who was making his home debut at the Parc des Princes following his blockbuster arrival from Barcelona, sat on the bench next to surprised team-mates.
Messi was involved in six shots (four attempts, two chances created) against Lyon and only Kylian Mbappe against Clermont (seven) has managed better in a league game so far this season for PSG.
A six-time Ballon d'Or winner, Messi also had 65 touches and made 48 passes with an accuracy of 83.3 per cent.
Pochettino told a post-match media conference: "I think everyone knows that we have many great players, with a 35-man squad.
"We have to make choices, within the matchday squad and then during the game, keeping in mind what's best for the team and every player.
"Sometimes the decisions are positive, or not, but that's what managers are there to do on the sidelines, to make decisions. It can please people or not.
"I asked him how he was and he said he was fine, no issues."
PSG secured victory over Lyon following a dramatic injury-time header from substitute Mauro Icardi from Mbappe's cross after Neymar's penalty had earlier cancelled out Lucas Paqueta's opening goal.
Pochettino's PSG are now five points clear of Marseille at the top of Ligue 1 after six wins from six games.
PSG has achieved a flawless start from its first six games for the third time after 2017-2018 and 2018-2019 – on both those occasions it went on to be crowned champion.
"It's very positive for us," Pochettino said of their start to the Ligue 1 campaign. "After the difficult game [against Club Brugge in the Champions League], this was important for us. Lyon are a very good team that play well.
"We conceded that goal in the second half. The team needed to show some character.
"We're in a period where we're trying a lot of things. We have to work on it in training, but it's difficult because we have a game every three days, and the priority is that the players recover.
"We can only do video sessions. It's not an excuse, we need to improve."