Messi was replaced by Achraf Hakimi, a full-back, after 76 minutes against Lyon, on his first home appearance as a PSG player since arriving from Barcelona.
The 34-year-old appeared to reject Pochettino's hand as he walked past his coach towards the Paris bench but the former Tottenham Hotspur boss later defended his decision to take Messi off without mentioning the injury.
On Tuesday he admitted that Messi's fitness was the reason he made the change with the scores level at the time.
"On the touchline we are always observing the players, seeing what is happening during the match, and we saw that Leo was looking at his knee," Pochettino told reporters.
"We are pleased with the way he played. He played very well in the first half, and the only thing missing was a goal.
"He played for 76 minutes and with all the information we had we decided to take him off," added Pochettino, who said he accepted that substituting a player of Messi's status might surprise observers.
"Of course I understand the situation and I accept it as it is.
'Best thing for him'
"It is not a surprise for me, but the priority is always the well-being of the player and in this case we thought it was the best thing for him to take him off.
"All great champions always want to be on the pitch and that is understandable."
Mauro Icardi's stoppage-time headed goal secured victory for PSG against Lyon, leaving them with six wins out of six in Ligue 1 this season and already five points clear of second-placed Marseille, albeit having played a game more.
They will be expected to keep their run going away to a Metz side who are winless and prop up the division, although Pochettino may heavily rotate his squad.
PSG are at home to Montpellier at the weekend, when it remains to be seen if Messi will return. They then host Manchester City in the Champions League next Tuesday, 28 September.
"We have a squad of 35 players. They all deserve to play but there are not enough places," admitted Pochettino.
The Argentine manager has also come in for criticism for the way his all-star team played against Lyon and in last week's 1-1 draw at Club Brugge in the Champions League.
Those were the first two matches in which Messi, Neymar and Kylian Mbappe had all played together, but Pochettino says he needs time to get his ideas across.
"In general, in the past, in normal times, you had six or seven weeks in pre-season, lots of friendly matches to work on things.
"Now we need to try things as we go along, during games. It is not a situation we like much but we have to get used to it."
There is a full round of games in France on Wednesday with Marseille aiming to continue their unbeaten start away at Angers.