The 23-year-old was forced off with a suspected ankle injury, during PSG's 4-0 Le Classique victory on Sunday night.
Mbappe was seen struggling with discomfort following a tackle from Leonardo Balerdi.
The World Cup winner hobbled off the pitch to receive treatment, before eventually returning.
Though he did not last much longer, substituted on 32 minutes, before heading straight down the tunnel at the Parc des Princes.
He is now a doubt for the Ligue 1 champions' clash with Newcastle at St James' Park next week.
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It is certainly a big concern for boss Luis Enrique, with his talisman netting seven goals in just four Ligue 1 appearances prior to Le Classique.
Achraf Hakimi scored a sublime free-kick on eight minutes to open the scoring on the night, before Randal Kolo Muani added a second after half-time.
Mbappe's replacement Goncalo Ramos then netted twice to complete the rout.
It remains to be seen the seriousness of Mbappe's injury, but the Parisian giants will hope to have him back in time to face Newcastle.
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Following the win, PSG now sit third in Ligue 1 behind Brest and Nice, and face Clermont in the league.
They then travel to the north East for their Champions League encounter against Eddie Howe's side on October 4.