The 24-year-old had to come off after 21 minutes at the Stade de la Mosson, having ostensibly damaged his hamstring following a challenge from Leo Leroy.
Christophe Galtier's side, who also lost Sergio Ramos to a head injury in the first half, managed to claim a 3-1 victory without Mbappe, and the PSG boss was inevitably asked about his condition after the game.
Galtier initially cut an upbeat figure and was confident that Mbappe had not suffered a serious injury, telling Canal+: "He took a knock to the back of the knee or the back of the thigh, so we'll see. I'm not too worried.
"It's a bruise or a contusion, we don't know yet. With the run of matches we don't want to take risks with a very busy fixture list, but it doesn't appear that serious."
However, having undergone scans on the problem on Thursday, PSG have now confirmed that Mbappe will spend approximately three weeks on the sidelines, meaning that he will miss Les Parisiens' opening clash against Bayern.
"After undergoing tests, Kylian Mbappé suffered an injury to the left thigh at the level of the femoral biceps. He is expected to be out of action for three weeks," a statement read.
Galtier's side welcome Bayern, who beat them in the 2019-20 Champions League final, to the Parc des Princes for their last-16 first leg on February 14, and Mbappe is also set to miss a number of key domestic fixtures.
PSG and Marseille will do battle in Le Classique on February 8 for their Coupe de France last-16 tie, either side of Ligue 1 games with an in-form Toulouse this weekend and Monaco on February 11.
Following the visit of Bayern, PSG will host Lille on February 19 in Ligue 1 before another meeting with Classique rivals Marseille at the Orange Velodrome on February 26, which Mbappe will aim to come back for.
The France international is joined in the treatment room by fellow attacker Neymar, who was absent from Wednesday's win over Montpellier due to muscular fatigue.
Nordi Mukiele (hamstring) and Presnel Kimpembe (Achilles) also remain absent for the French champions, who added that Ramos would undergo further tests after coming off with a head injury at the Stade de la Mosson.
Prior to Mbappe's enforced substitution, the striker had a penalty saved by Benjamin Lecomte before a retake was awarded, but his second attempt hit the post and he blazed the rebound over the bar from close range.
Galtier's side recovered from a slow first half to strike through Fabian Ruiz and Lionel Messi in the second 45 before Arnaud Nordin pulled one back for Montpellier, but Warren Zaire-Emery added a third to become PSG's youngest-ever goalscorer at 16 years and 330 days.
Les Parisiens now hold a five-point lead over Marseille at the top of the table and welcome Toulouse to the Parc des Princes on Saturday afternoon.