The Blues have not played a top-flight fixture since September 3, when they controversially prevailed by a 2-1 scoreline against West Ham United.
Since then, Graham Potter has replaced Thomas Tuchel in the dugout, and the Englishman will be eager to get off to a winning start with Chelsea down in seventh position in the standings, albeit with a game in hand on some of the clubs above them.
Here, Sports Mole rounds up Chelsea's latest injury and suspension news ahead of their short trip to Selhurst Park.
N'Golo Kante
Status: Minor doubt
Type of injury: Hamstring
Possible return date: October 1 (vs. Palace)
N'Golo Kante has not made an appearance for Chelsea since sustaining a hamstring injury against Tottenham Hotspur on August 14. However, the Frenchman made a welcome return to training earlier this week, and Potter may feel that the midfielder is fit enough to take a spot on the substitutes' bench.
Nevertheless, a return versus AC Milan next week feels more likely given the importance of the fixture in the Champions League.
Edouard Mendy
Status: Minor doubt
Type of injury: Knee
Possible return date: October 1 (vs. Palace)
An issue with his knee has kept Edouard Mendy on the sidelines for the last two fixtures, both of which came in the Champions League. However, the Senegalese goalkeeper featured on the training pitch earlier this week, despite having not being fit enough to represent his country on international duty.
CHELSEA'S SUSPENSION LIST
Chelsea have no players suspended for this London derby.