Trailing 1-0 from the first leg, Simeone will welcome two defenders back who did not play in Bucharest, as Kieran Trippier has now served a 10-week suspension while Jose Gimenez has successfully shaken off a muscular problem.
There were initial concerns over the fitness of Jan Oblak before the weekend's showdown with Getafe, but the Chelsea-linked shot-stopper started and kept a clean sheet in that game and is raring to go for the second leg.
Saul Niguez lasted just 45 minutes of Saturday's goalless stalemate with Getafe but is in no danger of losing his place in the engine room, and his fellow Spaniards Koke and Marcos Llorente will also be tasked with pulling the strings in the English capital.
As a result, Arsenal loanee Lucas Torreira is expected to be benched upon his return to London, but attacker Joao Felix is expected to return to the first XI after he was named among the substitutes last time out in the league.
Luis Suarez has gone from strength to strength in the top flight this term, but he is yet to get off the mark in the Champions League and will be desperate to score away from home in the tournament for the first time since September 2015 this week.
Atletico Madrid possible starting lineup:
Oblak; Trippier, Gimenez, Savic, Lodi; Koke; Felix, Llorente, Saul, Correa; Suarez