Mbappe picked up his fifth booking of the season against Monaco in PSG's last league game, ruling him out of their final match before the winter break.
Marco Verratti suffered the same fate against Monaco too and will therefore also be ineligible for the midweek meeting with a woefully out-of-form Lorient side.
The key duo join Neymar on the sidelines as the Brazilian continues to recover from an ankle injury, but the other member of the fearsome front three - seven-time Ballon d'Or winner Lionel Messi - is available to start.
Juan Bernat was withdrawn five minutes into the second half of the win over Monaco and remains sidelined with the hamstring injury he sustained, while Nuno Mendes is expected to miss out with a calf problem.
Abdou Diallo could be forced out to left-back as a result, which could see Sergio Ramos handed just his second league start for the club in the middle - although Presnel Kimpembe provides an alternative option to partner Marquinhos.
Wednesday's match is likely to come too soon for Julian Draxler to return, but Leandro Paredes could retain his place from the weekend Coupe de France win, with either Idrissa Gueye or Georginio Wijnaldum dropping into the holding midfield role in Verratti's absence.
Paris Saint-Germain possible starting lineup: Navas; Hakimi, Ramos, Marquinhos, Diallo; Gueye, Wijnaldum, Paredes; Messi, Icardi, Di Maria body check tags ::