Messi was outstanding in the first half at the Parc des Princes but began to fade after the break and was replaced by Achraf Hakimi for the final quarter-of-an-hour with the score at 1-1.
A stoppage-time header courtesy of substitute Mauro Icardi sealed a 2-1 comeback win for PSG.
"Everyone knows we have great players, a squad of 35. It is my decision. We can only have 11 players on the field at one time," Pochettino said.
"I only think about the best decision in each game, for each player, just as every coach does.
"We are here to make decisions. Sometimes people will be happy with them, sometimes they won't be."
Messi appeared to fall into the latter category, rejecting Pochettino's hand as he walked past his coach towards the Paris bench.
Pochettino dismissed any suggestion the six-time Ballon d'Or winner was unhappy, saying: "I asked him how he was and he said he was fine."
Messi, who hit the woodwork from a free-kick in the first half, is still looking for his first goal since his shock switch to Paris from Barca.
The excellent Lucas Paqueta gave Lyon the lead in the 54th minute, before Neymar won and then converted from the spot midway through the second half of an absorbing contest at the Parc des Princes.
"We deserved our victory, even if it was in the last second," insisted PSG coach Mauricio Pochettino.
The victory maintained PSG's perfect start in Ligue 1 with six wins from six this season and they are now five points clear at the top from Marseille.
Lyon are already 10 points behind the leaders in ninth place.