Koke is facing a spell out with a hamstring problem, while Geoffrey Kondogbia has made the move to Marseille, and the Red and Whites are currently lacking numbers in the middle of the park.
Atletico have made four signings this summer but all of them have been defenders, with Javi Galan, Santiago Mourino, Caglar Soyuncu and Cesar Azpilicueta moving to Wanda Metropolitano.
Speaking ahead of Sunday's La Liga clash with Real Betis, Simeone addressed the need to sign a central midfielder before the end of the transfer market.
"It's clear that if we reinforce ourselves we will be boosted as it would cover an area that's a little unprotected," the Argentine told reporters during his press conference.
"With a new midfielder we would complete what the team needs to compete in the best way."
Pablo Barrios had been an injury doubt for Sunday's game with Real Betis, but Simeone has confirmed that the 20-year-old will be available for selection in a midfield boost.
"Beyond Koke, we have the option of Barrios as he recovered for tomorrow (Sunday). He will be in the squad, and there is also the possibility of a Plan B," added the head coach.
Thomas Lemar operated alongside Rodrigo De Paul and Koke in midfield against Granada last weekend, before Barrios was introduced off the bench as Koke's replacement.
Rodrigo Riquelme is also an option, with the 23-year-old said to be staying with Atletico this summer despite a host of speculation surrounding his future.
According to Marca, 23 clubs have shown an interest in the midfielder this summer, with Napoli and Manchester City among those keen on his services.
However, Simeone's side have allegedly made it clear that the former Spain Under-21s international will be remaining at Wanda Metropolitano this season.
Riquelme impressed on loan at Girona last term, making 35 appearances in all competitions, while he has also had short-term spells with Bournemouth and Mirandes.
Tottenham Hotspur's Pierre-Emile Hojbjerg is thought to be Atletico's leading midfield target this summer, but the Denmark international's asking price is believed to be problematic for the Red and Whites.