The international break has not been helpful to Diego Simeone's side, who not only will face the match without Suarez, but his Uruguayan compatriot Lucas Torreira. Hector Herrera was also injured on international duty and will miss out.
Simeone is likely to play an attacking team in any event, with Marcos Llorente and the in-form Joao Felix being joined in attack by Angel Correa.
Ansu Fati's long-term injury will keep him out until March, and while Philippe Coutinho has returned to training, this match may come too soon for him.
Which means Lionel Messi playing off Antoine Griezmann as the central striker, and Ousmane Dembele will likely get to start from his preferred left-hand side, with either Pedri or Francisco Trincao on the right - likely the former.
Taking Busquets' place in the double pivot will be Miralem Pjanic who will partner Frenkie De Jong.