The result also means second-placed Real Sociedad can reclaim top spot if they beat Eibar on Sunday.
Diego Simeone may not have the stomach to reinvent Atletico Madrid again after they suffered another morale-shattering loss to Real Madrid in Saturday's Champions League final.
Atletico Madrid fell to their heaviest league defeat of the season
Heavyweights Arsenal, Atletico Madrid and Lazio took big steps towards reaching the Europa League semi-finals after convincing home first-leg victories and RB Leipzig also stayed on course with a 1-0 win over Olympique de Marseille on Thursday.
Real Madrid's Gareth Bale came off the bench and coolly converted a controversial penalty to secure a 2-1 win at Levante in La Liga on Sunday as the European champions rode their luck to stay within nine points of leaders Barcelona.
Former champions Atletico de Kolkata notched up their first victory of the tournament with a 1-0 win over Kerala Blasters FC in the Indian Super League football match at Jawaharlal Nehru Stadium in Kochi, on Wednesday.
If Atletico Madrid's 2013 King's Cup triumph was a shock and their 2013-14 La Liga title a surprise, few would raise an eyebrow if Diego Simeone's ruthlessly efficient side were to win another major trophy.
Second-half headers from Diego Godin and Raul Garcia gave holders Atletico Madrid a 2-0 win over Valencia and a place in the King's Cup quarter-finals by 3-1 on aggregate.
News of all that's transpired on and off the football field
Atletico Madrid made a typically aggressive start to lay the foundations for a 2-0 victory at home.
A first half Tiago header set up Atletico Madrid's 2-0 victory over Espanyol as they seek to get back on track following a stuttering start to the La Liga season.
Real moved to 57 points, two ahead Girona and 10 clear of Atletico Madrid and Barcelona.
Goalkeeper Ivan Provedel scored in the dying moments of the Champions League Group E match against Atletico Madrid, heading home the equaliser, to earn Lazio a 1-1 draw at Stadio Olimpico, in Rome, on Tuesday.
Former Argentina international Carlos Tevez has been hospitalised due to chest pain, Club Atletico Independiente, the Argentine club he now coaches, said on Tuesday.
IMAGES from football matches played across Europe on Wednesday.
Atletico Madrid have been unable to repeat the magnificent achievements of last season in this campaign but can congratulate themselves on a job well done if they secure a lucrative Champions League berth on Saturday.
Atletico Madrid captain Gabi said his team would not be lulled into complacency by Barcelona's faltering form when they host the Champions League holders in the second leg of their quarter-final on Wednesday.
News of all that's transpired on and off the football field
A towering Diego Godin header secured Atletico Madrid a 1-1 draw against Barcelona and a first La Liga title for 18 years in a thrilling climax to the campaign on Saturday.
PSV Eindhoven played for more than 20 minutes with 10 men but held on for a goalless draw at home to Atletico Madrid in the first leg of their Champions League last-16 tie on Wednesday.
At the moment I don't see me having an expiry date, I'd love to stay here for many years to come, says Real Madrid manager Carlo Ancelotti, who'll be completing a landmark on Tuesday.
Libertadores Cup favourites Atletico Mineiro took a big step towards the quarter-finals with a 2-1 away win over 10-man Sao Paulo in the first leg of their last 16 tie on Thursday.
Champions Barcelona turned on the style to hammer Atletico Madrid 5-2 and consolidate their position at the top of the Spanish Primera Liga on Saturday. The visitors, who were thumped 6-1 in the same fixture last season, have yet to win a game in the new campaign but came out with an ambitious attacking lineup.
Inter Milan have completed the signing of Brazil centre back Miranda from Atletico Madrid as they look to shore up a defence that struggled during a disappointing 2014-15 season.
Real Madrid paid for defensive mistakes as they were held to a 3-3 draw at lowly local rivals Rayo Vallecano on Saturday.
Atletico Madrid have one foot in the final of the Europa League after a Radamel Falcao double fired the 2010 winners to a 4-2 semi-final first leg win at home to La Liga rivals Valencia on Thursday.
Atletico Madrid stayed firmly on course for a surprise La Liga title triumph when Raul Garcia's header secured a 1-0 win for the leaders at home to seventh-placed Villarreal on Saturday.
Lionel Messi scored a hat-trick as Barcelona clinched a 25th La Liga title on Sunday after winning 4-2 at Deportivo La Coruna despite throwing away a two-goal lead in a thrilling game which also confirmed Depor's relegation.
Atletico Madrid have moved to strengthen their forward line for next season following the exit of Mario Mandzukic by agreeing to buy Colombia striker Jackson Martinez from Porto.
'You realise the fear when Barcelona could get knocked out. It would hurt UEFA a lot. I don't know what they have to do for someone to send one of them off'
A downbeat Diego Simeone did not confirm whether he wanted to continue as Atletico Madrid coach on Saturday after suffering a second agonising Champions League final defeat by Real Madrid in three years.
Atletico Madrid cruised to a 3-0 home win over Real Sociedad on Tuesday to close the gap behind La Liga leaders Barcelona to five points.
Sergio Aguero scored a dramatic late winner as Atletico Madrid twice came from behind to stun visiting Barcelona 4-3 on Sunday, leaving the Catalans just four points clear at the top in Spain.
Diego Forlan is to leave La Liga club Atletico Madrid after four seasons and will join Serie A side Inter Milan, the Uruguay striker announced on Monday.
Ronaldo had failed to score in his last four league games for Real and his rotten run in front of goal looked set to continue when his spot-kick was turned away by visiting goalkeeper Roberto.
Property giant Dalian Wanda Group Co said on Wednesday it would buy a stake in Spanish soccer champions Atletico Madrid for 45 million euros ($52 million), becoming the first Chinese company to invest in a premier European football club.
Atletico Madrid have a chance to pile more King's Cup misery on neighbours Real after eliminating Athletic Bilbao on Wednesday to set up a last-four clash against the bitter city rivals they beat in last year's final.
While Real Madrid plot to clinch European Cup number 10, neighbours Atletico will look to thwart those plans.
Gareth Bale would not pick any Atletico Madrid player over one of his teammates, the Real Madrid forward said, as the two Spanish sides prepare to square off in Saturday's Champions League final. Atletico's defence conceded just 18 goals last season in the league, fewer per game than any other team in Europe's top five leagues. But when Bale was asked to create an ideal 11 from both teams, he said he would pick Real Madrid players every time. Asked by radio station Cadena Cope if he would pick Atletico's Jan Oblak, who equalled the La Liga record for the fewest goals in a season, or Real's Keylor Navas, Bale said, "Keylor, 100 percent." Asked which side had the best midfield and defence, he added: "Real Madrid, everyone Real Madrid."
