Koke will miss Sunday's trip to Vigo after picking up a hamstring injury in the champions' 4-0 hammering of Real Madrid last week, while Arda Turan and Raul Garcia are banned after collecting their fifth bookings of the season in the derby.
Third-placed Atletico play after both Real and Barcelona this weekend and, with their title rivals facing what are - on paper at least - straightforward home games against Deportivo La Coruna and Levante, three points at the Estadio de Balaidos is crucial for Simeone's side.
And the Argentinian has called on his team to pick up the collective slack left by the enforced absences of Koke, Arda and Garcia.
"You all know what Koke and Arda provide us with - creativity, talent and the fact they are used to our style of play and also the variety we have with them on the pitch," Simeone told his pre-match media briefing on Saturday.
"Their absences, along with Raul Garcia's, generate an extra effort for the team to neutralise such important absences.
"Because, as I always say, you don't need a team to compete in the best way - with a team, you can win certain games [but] to compete seriously, you need a group.
"The guys that are working here, they do it in order to make the most of the chances they get.
"Hopefully everything will work out."
