Diego Simeone's side have faltered in recent weeks, winning only one of their last four games, although they do still sit at the top of the league with a game in hand on the chasing sides, while the hosts will be looking to end a run of six La Liga games without a win.
Unai Emery's side progressed to the final 16 of the Europa League last time out as they saw off Red Bull Salzburg in the second leg of their round-of-32 tie.
The Yellow Submarine came into the tie with a 2-0 aggregate lead, but that was put under pressure when Mergim Berisha scored early for the Austrian outfit, before Gerard Moreno found the net after 40 minutes to restore Villarreal's two-goal cushion.
The Spaniard then scored his second of the game late on, to see his side cruise through to the next round of the European competition with a fairly comfortable 4-1 aggregate victory over the Austrian champions.
However, their recent league form has been much more worrying, having failed to pick up a victory from their last six games in the top flight, dropping down to sixth spot after they previously sat in third.
Emery's side drew 1-1 away at Athletic Bilbao in their last league game, when Alex Berenguer equalised for the hosts after Moreno gave Villarreal an early lead.
They will be hoping to get back to winning ways here, but that will be no easy task as they take on the league leaders.
The side from Madrid come into this game having lost their last two matches, most recently falling to a 1-0 defeat in the 'home' leg of their Champions League round-of-16 tie with Chelsea, which took place in Romania.
In typical Diego Simeone style, Atleti set up in a defensive shape, and they looked to grind out a clean sheet until Olivier Giroud found the net with an eye-catching overhead kick to give the English outfit a 1-0 lead going into the second leg.
Before that, Los Colchoneros played consecutive La Liga games against Levante, picking up just one point from the two outings.
The most recent fixture resulted in a 2-0 loss for Atleti, when Jose Luis Morales had an effort deflected in off Mario Hermoso after half an hour, before the game was sealed deep into added time when Jorge de Frutos put the ball into an empty net after Jan Oblak had gone up for a late set piece.
They now sit just three points ahead of city rivals Real Madrid, however Simeone's side do still have a game in hand on Los Blancos.
He will be desperate to get back to winning ways here to increase that gap further, before Zinedine Zidane's men play on Monday night.
Villarreal La Liga form: DDDDLD
Villarreal form (all competitions): LDLWDW
Atletico Madrid La Liga form: WWDWDL
Atletico Madrid form (all competitions): WDWDLL
Gerard Moreno will feature up front, having scored 14 league goals this campaign, alongside Paco Alcacer.
Atletico Madrid are expected to be without centre-back Jose Gimenez for this game after he missed the Champions League tie with Chelsea following an injury picked up in the defeat to Levante.
They will also be without Kieran Trippier, who continues his ban after breaking gambling rules.
Their line will be led by Luis Suarez, who has netted 16 goals from 20 league games since his summer move from Barcelona.
Villarreal possible starting lineup:
Asenjo; Costa, Albiol, Torres, Alfonso; Trigueros, Capoue, Parejo, Gomez; Alcacer, Moreno
Atletico Madrid possible starting lineup:
Oblak; Savic, Felipe, Hermoso; Llorente, Saul, Koke, Lemar; Correa, Suarez, Felix
We say: Villarreal 1-1 Atletico Madrid
Although Villarreal have struggled to find league wins recently, we see Atletico's run of disappointing form continuing here, with the sides sharing the points at the Estadio de la Ceramica.
Their recent attacking struggles, coupled with a strong defence coming up against Villarreal's promising front line, should result in a low-scoring draw, as the league leaders continue to drop points and face further pressure from the chasing pack.