Atletico currently occupy second place in the league table, with seven points separating them from leaders Barcelona. If they are to claw back the deficit and secure an 11th championship title against the odds, they must pick up victories against sides like Bilbao (and hope the Champions League campaign takes its toll on Barça).
Their hosts languish in mid-table obscurity and have just two wins in their previous six league matches. Simeone will view this as a decent opportunity to move on from Tuesdays Champions League exit at the hands of Juventus and to readjust the teams focus to domestic matters.
Heres the side he may field for Saturdays encounter.
3. Goalkeeper & Defenders
Jan Oblak (GK) - The Slovenian is a vital component in Simeones exceptional defensive setup. His reflexes and positional sense are superb, giving those in front huge amounts of confidence.
Santiago Arias (RB) - With Filipe Luis and Lucas Hernandez both sidelined, the Colombian has been afforded more game time in recent weeks. Unfortunately, he was below par during the 3-0 defeat in Turin, unable to cope with the traffic down his flank.
José Giménez (CB) - The Uruguayan has forged a remarkably strong partnership with his fellow countryman. Now in his sixth year under Godins tutelage, Giménez looks ready to fill the space that will be left when his mentor departs.
Diego Godin (CB) - At 33 and with his contract expiring in June, these could be Godins final few months in the Spanish capital. Once again he has been a rock for Atletico, offering consistency, passion and composure in equal measure.
Juanfran (LB) - The minor left-back crisis has seen Juanfran switched to the opposing full-back berth. He was another who failed to perform to his best against Juventus, though he was faced with the unenviable task of shackling Cristiano Ronaldo and the lively Federico Bernardeschi.
Koke (RM) - The Spanish midfielder had few opportunities to showcase his creativity and ball-playing skills at Allianz Stadium as Atletico sat back. His tally of four goals and two assists sees him sitting second in the clubs scoring charts this season.
Thomas (CM) - After working his way through the youth setup the Ghanaian has now established himself at the Wanda Metropolitano. His energy, work ethic and tough tackling make him well-suited to Simeones style of play.
Saúl (CM) - One of the most sought after playmakers in Europe, Saúl is pivotal for his team. His teammates will be hoping he can find a way past Bilbaos outstanding Iñigo Martínez in central defence.
Thomas Lemar (LM) - The tricky French winger was purchased for north of £60m last summer and has not quite lived up to the billing in La Liga. However, he is just 23 years old and has offered glimpses of his supreme talent for Los Rojiblancos.
Antoine Griezmann (CF) - With 16 goals and nine assists in all competitions this campaign, Griezmann has been Simeones primary attacking force. His agility, nerveless finishing and ability to link up with his fellow forwards will have Bilbaos backline on high alert.
Nikola Kalinić (ST) - After Alvaro Moratas lacklustre showing against his old side in midweek, Kalinić is likely to be given a chance to lead the line. He has been underwhelming this year and will hope to rediscover some form in the Basque country.