A place in the quarter-finals is up for grabs with the game level at 1-1 after the first leg in Spain.
Sime Vrsaljko, Daniel Wass, Thomas Lemar and Matheus Cunha will be absent for Atletico at Old Trafford.
But Simeone is expected to have Geoffrey Kondogbia, Mario Hermoso and Jose Maria Gimenez available for selection after traveling with the squad amid injury concerns.
Centre-back Gimenez came off late in Friday’s win over Cadiz but dismissed any concerns over a muscle problem.
Marcos Llorente should continue to replace Vrsaljko at right-back in Los Rojiblancos’ 3-5-2 formation. Renan Lodi is expected to enter on the left flank amid Yannick Carrasco’s suspension.
Kondogbia and Hermoso, as well as Angel Correa, hope to return to the XI while Luis Suarez is expected to be named on the bench.
Atletico Madrid starting XI predicted: Oblak; Llorente, Savic, Giménez, Reinildo, Lodi; Koke, Herrera, Kondogbia; Felix, Griezmann.