Ahead of the trip to England on Wednesday night, PSG announced that the duo have not been able to recover from their injuries.
Kimpembe had been out of action after suffering an Achilles injury in February and has not featured since.
The good news for the Paris team is that the Frenchman is nearing his return, although not quickly enough to feature at St James’ Park.
Asensio is also expected to return to action as his injury is not long-term.
The Spaniard, who joined PSG as a free agent last summer, got injured on international duty. Spain national team coach Luis de la Fuente had said that Asensio could be absent until the next international break in mid-October.
According to reports, Asensio could feature against Stade Rennais on Sunday.
PSG will also be without Lee Kang-in, who is still on international duty with South Korea, while Cher Ndour, Layvin Kurzawa, and Hugo Ekitiké are not registered for the Champions League.
PSG currently top their league after opening their Champions League campaign with a win against Borussia Dortmund, while Newcastle held AC Milan to a stalemate at the San Siro two weeks ago.
Luis Enrique’s side currently have 12 points from their first seven league game and are fifth on the log.
They are going into this clash on the back of a draw away at Clermont Foot.
On the other hand, Newcastle are confident after defeating English champions Manchester City during the midweek Carabao Cup clash and a 2-0 win at St. James against 2inless Burnley in the Premier League.
PSG will hope to continue their good run in the competition, while Newcastle, returning to Europe after 20 years of absence, will have to prove themselves against the French champions.