Both defenders are out through suspension, with Trippier set to miss Atletico's next 13 games due to his suspension by the English FA for betting related breaches.
Simeone therefore will have to re-juggle his backline ahead of the game.
Simeone is expected to utilise a 4-3-3 system. Jose Gimenez, Felipe, Mario Hermoso and Sime Vrsaljko will play across the back.
Croatian defender Ivo Grbic is out through injury.
In midfield, Simeone will deploy Atletico stalwarts Koke and Saul Miguez. Yannick Carrasco will also slot into the last midfield place.
Marcos Llorente, Luis Suarez and Joao Felix will start in the attacking berths for Simeone's side.
The three have scored a total of 18 goals in La Liga for Atleti this season, and need to continue their fine form if they are to maintain their lead at the tip of the table.
Atletico are currently two points clear of city rivals Real in La Liga.