Mbappe appeared to hurt his left leg in a tangle with Marseille defender Leonardo Balerdi, in which his ankle turned, just seven minutes into the match at the Parc des Princes.
PSG were awarded a free-kick from which Achraf Hakimi put them in front, before Mbappe went off the pitch for treatment.
He briefly returned to the field and then came off again, removing his left boot and consulting the team doctor.
The France superstar then attempted to carry on but gave up and walked off looking in some discomfort to be replaced by Goncalo Ramos in the 31st minute.
Mbappe had scored eight goals in five appearances for PSG in this campaign prior to Sunday, since returning to the first-team fold following a contract dispute during the close season.
