Mbappe picked up a thigh injury and went off after 21 minutes in PSG's 3-1 win at Montpellier on Wednesday.
The injury capped a frustrating night for the 24-year-old, who also missed two penalties and put a rebound over the bar.
PSG boss Christophe Galtier remained upbeat about Mbappe's injury after the game, 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."
But Mbappe is set for a significant spell on the sidelines after PSG revealed he will miss three weeks of action.
"After undergoing tests, Kylian Mbappé suffered an injury to the left thigh at the level of the femoral biceps," they wrote in a brief statement.
"He is expected to be out of action for three weeks."
PSG will host Bayern Munich in the first leg of their round of 16 tie on February 14.
Before then Mbappe will miss league matches against Toulouse, Monaco and Lille as well as a Coupe de France clash with Olympique Marseille.
Mbappe has scored 25 goals in 26 appearances across all competitions for PSG this season.