Real Madrid will be expected to overcome Olimpic de Xativa in their Copa del Rey second leg despite being held to a draw away from home.
In the third tier in Spain, Toni Aparicio's men surprisingly held Real to a 0-0 draw in the first leg of the last-32 tie at the Estadio La Murta.
Carlo Ancelotti had the likes of Angel Di Maria and Isco in his starting line-up for the clash but they failed to find a goal away from home and need to increase their intensity after a lacklustre week, which has included draws versus Olimpic and Osasuna.
A trip to the Santiago Bernabeu shapes as a daunting test for Olimpic, even if Real are again without superstars Cristiano Ronaldo and Gareth Bale.
The visitors will need plenty of luck and it would be a huge shock if Ancelotti's men, third in La Liga after a 2-2 draw against Osasuna on Saturday, failed to progress.
Elsewhere, Barcelona host Cartagena carrying a 4-1 lead from the first leg after surprisingly falling behind to the Segunda B side.
Gerardo Martino is likely to rest several of his regulars with such a big advantage heading to the Camp Nou.
Reigning champions Atletico Madrid should do the same as they prepare to welcome Sant Andreu after winning the opening leg 4-0.
Several other top-flight teams have work to do if they are to advance to the last 16.
Relegation-threatened La Liga side Real Betis lead Segunda B outfit Lleida Esportiu 2-1 ahead of a home clash.
Real Sociedad only claimed a 1-1 first-leg draw versus Algeciras, while Getafe host Girona after their match finished with the same scoreline.
Levante trail second-tier Recreativo Huelva 1-0, Valencia were held 0-0 by another Segunda B team in Gimnastic Tarragona and Espanyol host Real Jaen after their 2-2 draw.
An all-La Liga tie between Elche and Villarreal is locked at 2-2 ahead of a meeting at the Estadio Manuel Martinez Valero, while Real Vallecano and Real Valladolid drew their opener 0-0.
Sevilla lead Racing Santander 1-0 and Athletic Bilbao must overturn a 1-0 deficit when they host Celta de Vigo.
Granada welcome Alcorcon with a 2-0 advantage, Almeria host Las Palmas leading 3-1 and Osasuna and Malaga meet after a thrilling 3-3 draw first-up.
|22||Á. di María||27'|
|Coach: C. Ancelotti|
for Illarramendi 58'
for Isco 69'
for Daniel Carvajal 76'
|Courtois: If nothing strange happens, I will continue at Chelsea|
|Vermaelen ´disappointed´ by Barca struggles|
|Higuain and Lamela dream of lifting the Copa America|
|Reborn Torres returns to Milan to complete Atletico´s greatest tale|
|Lukaku offers Everton ultimatum: I want to win trophies!|
|United States v Bolivia: Copa America hosts to fine-tune preparations|
|Zidane has united Real Madrid again - Ramos|
|Mexico v Paraguay: Marquez ready to make the most of ´great opportunity´|
|Coyle leaves Houston Dynamo|
|McLaren could end Mercedes dominance - Alonso|
|Orlando City 2 Philadelphia Union 2: Tribbett rescues point in controversial contest|
|United States 1 Ecuador 0: Last-gasp Nagbe goal lifts hosts in Copa America warm-up|
|Djourou compares Xhaka to Pirlo|
|Gallas ´very proud´ of former boss Ranieri´s title glory|
|Copa America to use goal-line technology|
|Smith likens Postecoglou to Klopp|
|Hart backs Sterling to shine at Euro 2016|
|Giovinco happy in MLS despite Euro 2016 snub|
|Balotelli set for Liverpool return, confirms Berlusconi|
|Atletico must win Champions League - Cerezo|
|Arbeloa: Mourinho didn´t get enough recognition at Madrid|
|Mijatovic: Bale can save Madrid´s season in Champions League final|
|Gallas expects Conte to revive Chelsea|
|Deschamps ´annoyed, but not worried´ by Varane´s absence|
|´Impossible´ to see MSN leaving Barcelona - Bartomeu|
|Thiago pledges future to Bayern|
|AFC Champions League Review: Urawa pay the penalty as Seoul advance|
|Uruguay v Trinidad and Tobago: Sanchez skips final to help Suarez-less La Celeste|
|Benitez ´convinced´ he can win trophies at Newcastle|
|Nigeria v Mali: Moses among many absentees for Super Eagles|
|Benitez to stay at Newcastle|
|Kramaric leaves Leicester for Hoffenheim permanently|
|Neustadter gets green light for Russia Euro 2016 selection|
|Chile v Jamaica: Copa plans crystallize in Vina del Mar|
|Ledley making progress in bid to prove Euro 2016 fitness|
|Gotze returns to Germany training|
|Ronaldo: Madrid would be smart to give me a new deal|
|Varane disappointed by Euros absence|
|Republic of Ireland v Netherlands: O´Neill wants confident display|
|Ronaldo shakes off injury in Real Madrid training|
|Atletico star Griezmann ´listening to different clubs´|
|United States - Ecuador Preview: Klinsmann pins hopes on Yedlin as Copa preparations continue|
|Gold tells Middlesbrough to ´dream on´ over Antonio|
|Schweinsteiger wants Mourinho to spice up Manchester derby|
|England v Australia: All eyes on Rashford debut|
|Aggressive Premier League better for me - Xhaka|
|Schweinsteiger ´right on schedule´ for Euro 2016|
|Darmian relishing Euros after return from injury|
|Northern Ireland v Belarus: Last chance to impress as O´Neill prepares to trim squad|
|Ventura leaves Torino amid Italy talk, Mihajlovic appointed|
|Sevilla confident of keeping Emery|
|Godin wants Atletico to use 2014 defeat as inspiration|
|Xhaka agrees Arsenal move|
|Idolisation of Ibrahimovic warranted Sweden captaincy - Hamren|
|Scholes hopes Mourinho keeps Giggs at Manchester United|
|Gotze snubbing Liverpool will boost Germany - Bierhoff|
|Bosz honoured by Ajax appointment|
|Ramos highlights Griezmann threat|
|Record-chasing Ronaldo and taming the Wolves - Real Madrid´s route to the Champions League final|
|Donnarumma dreams of being Milan captain|
|Koke: History, not revenge motivating Atletico|
|Costa Rica v Venezuela: Hosts ramp up preparations for maiden Copa America tilt|
|Argentina v Honduras: Messi and co warm up for Copa America|
|USA will win a World Cup, says Donovan|
|Pumas UNAM 2 Independiente del Valle 1 (3-3 agg, 3-5 on penalties): Hosts suffer shoot-out heartbrea|
|Gracia leaves Malaga as Rubin Kazan loom|
|Messi: Argentina deserve to be Copa America champions|
|Dybala included in Argentina´s preliminary Olympics squad|
|Mourinho and United a ´good wedding´ - Ancelotti|
|Klinsmann: Copa America better than Euros|
|Messi: Joining Barcelona not an easy decision|
|Carrico receives four-game ban for homophobic slur|
|Dani Alves wants Atletico to win Champions League|
|McNair out to impress ´world-class´ Mourinho|
|Ranieri: Premier League survival is Leicester´s priority next season|
|Argentina forward Lavezzi suffers hamstring scare|
|Koeman talks ´very positive´, say Southampton|
|Rami replaces injured Varane in France´s Euro 2016 squad|
|Matthaus applauds Gotze for rejecting ´easy solution´ of Liverpool|
|Suarez silenced his doubters - De Boer|
|AFC Champions League Review: Jeonbuk, Shanghai SIPG progress|
|Klopp can take Liverpool right to the top, says McAllister|
|Lindelof happy at Benfica amid Real Madrid, Barcelona links|
|Zidane is perfect on and off the pitch - Lippi|
|Bale: Zidane has brought the best out of Real Madrid|
|Favre takes over as Puel and Nice part ways|
|Liverpool complete Karius deal|
|Van Gaal was treated poorly by United, but Mourinho will be a success - De Boer|
|Dani Alves: I have won more titles than Pele|
|I know who I´m taking - Conte sure on Euro 2016 selection|
|Xavi backs Guardiola to ´change the face of English football´|
|Lucescu appointed Zenit boss|
|Manchester United and Liverpool hit with €40,000 fines|
|Weinzierl: I have nothing to lose at Schalke|
|Rangers complete Barton signing|
|Italy better placed as underdogs ahead of Euro´s - Motta|
|Cantona: I love Mourinho, but he is not Manchester United|
|Ben Arfa wants Lyon move - Aulas|
|David Silva praises Iniesta´s Copa del Rey heroics|
|´It was a little scare´ - Ronaldo plays down injury fears|
|Eder the real deal for Lille|
|Van Gaal treated unfairly during Manchester United spell - Daley Blind|
|Ginola doing ´very well´ after heart surgery|
|Depay rules out Manchester United exit following Van Gaal departure|
|Hojbjerg confirms desire to leave Bayern|
|Ronaldo leaves Madrid training early after knock|
|Abbiati unimpressed with Milan players´ attitude|
|Pepe calls on Madrid to continue making history|
|Ayestaran signs two-year deal with Valencia|
|Montolivo, Antonelli sign new AC Milan contracts|
|Ronaldo ready for UCL final after being rested from practice match|
|Hummels, Sanches deals will not stop Bayern spending - Rummenigge|
|Oblak´s penalty heroics, Griezmann´s Barcelona brace - Atletico Madrid´s route to the Champions Leag|
|Salvio all but confirms Gaitan will join Atletico Madrid|
|Motta warns PSG over Ronaldo, Neymar interest|
|Europa League Mourinho´s best hope for United trophy - Sheringham|
|Injustice if Iniesta never wins a Ballon d´Or - Del Bosque|
|Van Gaal didn´t deserve United sacking - Blind|
|I´ll be happy if we make Euro 2016 semi-finals - Del Bosque|
|Koke: Why would I want to leave Atletico?|
|Fofana could retire aged 25 - Lyon president|
|Sandro set to leave Barcelona|
|Silva plays down injury worries ahead of Euro 2016|
|United would be brave to appoint Mourinho, says Schmeichel|
|Neymar adamant he is happy at Barcelona|
|Wilshere: Arsenal play me out of position|
|Ryan backs former coach Neville|
|Keane talks up Galaxy move for Ronaldo|
|´Free agent´ Diarra wants Mourinho reunion|