Atletico Madrid have already secured a place in the knockout stages for a fourth consecutive season.
Since Antoine Griezmann's stoppage time winner saw off FC Rostov three weeks ago and sealed Atletico's place in the knockout stages for a fourth consecutive season, back-to-back La Liga defeats to Real Sociedad and Real Madrid have left Atletico's title chances in tatters.
Indeed, finalists in two of the past three seasons, Atletico now even face a fight to qualify for next year's Champions League after slipping to sixth as Sevilla, Villarreal and Sociedad threaten their status as Spain's third force.
Yet, once again Atletico have proved themselves as a serious contender to finally deliver a first ever European Cup after becoming the first side to lose three finals without ever winning the trophy with a heartbreaking penalty shootout defeat to Real Madrid in May.
"They are once of the most respected teams on an international level, they are almost feared," said PSV midfielder Andres Guardado.
"They make matches seem very long. You need to make a huge effort and sacrifice to try and match their intensity and to damage one of the best defences in the world."
Atletico's defensive record has been the key to their contrasting form at home and in Europe so far this season.
In the Champions League they have remained watertight, conceding just once in four games.
However, Real's 3-0 win at the Vicente Calderon on Saturday was the first time Atletico had conceded three at home in the league since 2012 and the first time in Simeone's five-year reign Los Rojiblancos have failed to keep a clean sheet in five games.
With that in mind Simeone looks set to ring the changes for PSV's visit with Jose Maria Gimenez set to make his first appearance since September in central defence.
Sime Vrsaljko, Nico Gaitan and Kevin Gameiro are also expected to replace Juanfran, Saul Niguez and Fernando Torres from the side that started the derby against Real.
Atletico can seal top spot in Group D should they better Bayern Munich's result away to Rostov.
Bayern are also already through leaving PSV in a battle with the Russians to qualify for the Europa League in third with both only having taken one point so far.