Quique Setien's side played out a 1-1 draw with Celta Vigo in their most recent outing, while Los Blancos fell to a 3-1 loss to Barcelona in the final of the Supercopa de Espana.
Match preview
Embarking on a spectacular seven-game winning run in competitive and non-competitive fixtures leading up to their trip to Celta Vigo, Villarreal could not extend their victorious streak to eight matches, despite Gerard Moreno breaking the deadlock with only 15 minutes gone.
Jorgen Strand Larsen came off the bench to level for Celta Vigo in the second half, but there has been much to like about Villarreal since Setien succeeded Unai Emery, and regaining their rightful place in the Champions League is no longer mission impossible.
Indeed, the Yellow Submarine are sitting pretty in fifth in the La Liga table - only behind fourth-placed Atletico Madrid on goal difference - but at the same time only one goal separates Villarreal from fellow 28-pointers Real Betis in sixth spot.
The top-four race takes a backseat for the time being, as Villarreal - who have already beaten Santa Amalia, Guijuelo and FC Cartagena in this year's Copa del Rey - endeavour to make the quarter-finals of the competition for the third time in four seasons.
The Yellow Submarine have not progressed further than the last eight since losing to Barcelona in the 2014-15 semi-finals - their best-ever finish in the competition - but a first-ever piece of domestic silverware is long overdue for the Ceramica outfit.
Real Madrid make the journey to a team who have failed to keep a single clean sheet since the return of domestic football after the World Cup, but Carlo Ancelotti was left to rue defensive deficiencies as Barcelona clinched the Supercopa de Espana crown in Riyadh.
Gavi coolly slotted home the opening goal before turning provider for Robert Lewandowski and Pedri either side of the half time whistle, and Karim Benzema's response with only seconds remaining served as little consolation for the capital giants.
Also playing catch-up to La Blaugrana in the race for La Liga title glory, second-placed Real Madrid have a three-point gap to make up to Barcelona and face a particularly challenging set of fixtures against Athletic Bilbao, Real Sociedad and Valencia in the coming weeks.
It took a second-half goal from Rodrygo for Real Madrid to edge past Cacereno 1-0 in the last round of the Copa del Rey, which they have not won since 2014, and Los Blancos have suffered four quarter-final exits since last lifting the domestic prize nine years ago.
However, not since their last stint as defending champions in 2014-15 have Real Madrid been dumped out in the last 16, although they were beaten 2-1 by Villarreal at La Ceramica on January 7, and jet lag will not be the visitors' friend at the Yellow Submarine's fortress.
Villarreal Copa del Rey form:
W
W
Villarreal form (all competitions):
W
W
W
W
W
D
Real Madrid Copa del Rey form:
W
Real Madrid form (all competitions):
W
W
W
L
W
L
Team News
Villarreal boss Setien is facing a quandary at right-back for Thursday's game, as both Juan Foyth and Kiko Femenia - the latter of whom lasted just five minutes after replacing the Argentine - came off injured in the draw with Celta Vigo with shoulder and calf issues respectively.
It is unclear how severe the pair's injuries are, but they were both missing from training on Monday alongside Giovani Lo Celso, Alfonso Pedraza, Nicolas Jackson and Gerard Moreno, although the latter's absence was only believed to have been precautionary.
Arnaut Danjuma, who was an unused substitute at the weekend, recently travelled to England to hold transfer talks with unspecified clubs, and the Dutch winger is unlikely to be seen on the field on Thursday evening. Meanwhile, ex-Blancos man Raul Albiol is back from a ban and could start in the heart of the backline.
As for Real Madrid, right-back Lucas Vazquez is facing a few more weeks on the sidelines with a sprained ankle, while Aurelien Tchouameni and David Alaba both missed the Supercopa de Espana tournament with calf injuries, and their availability here is up in the air.
Amid an unforgiving winter schedule and long journey home from the Middle East, Ancelotti should not be averse to making several alterations, starting with Andriy Lunin possibly enjoying a run-out in goal over Thibaut Courtois.
The fresh legs of Rodrygo and Marco Asensio could also come in handy in attack, while Dani Ceballos is a candidate to come into the engine room if Luka Modric is given the night off.
Villarreal possible starting lineup:
Reina; Cuenca, Albiol, Torres, A. Moreno; Capoue, Morlanes, Parejo; Chukwueze, Moreno, Pino
Real Madrid possible starting lineup:
Courtois; Carvajal, Militao, Nacho, Mendy; Kroos, Camavinga, Ceballos; Rodrygo, Benzema, Vinicius Jr
We say: Villarreal 2-1 Real Madrid
Lightning may very well strike twice at La Ceramica this week, with plenty of Ancelotti's first-team crop under-performing, others out injured and nearly all battling the effects of a tiring mid-season trip for the Super Cup.