Real Madrid's season hit yet another stumbling block, as a 93rd-minute goal from Gerard Moreno handed Espanyol a famous win over a Ronaldo-less Los Blancos.
Both sides enjoyed spells of pressure in a game that looked destined to end goalless, before Moreno's late intervention handed Los Blancos a fifth defeat of the season. The defeat leaves Zidane's men 14 points behind league leaders Barcelona and seven behind city rivals Atletico Madrid.
Espanyol manager Quique Sanchez Flores made two changes from the side that were held to a goalless draw by relegation threatened Deportivo on Friday night, with Marc Navarro and Sergio Garcia replacing Esteban Granero and Leo Baptistao.
With Zinedine Zidane opting to rest Cristiano Ronaldo and Karim Benzema dropping to the bench, it was Isco and Marco Asensio brought into the attacking fold. Marco Llorente took Casemiro's place in the midfield, while Sergio Ramos and Achraf Hakimi lined up in defense, replacing Dani Carvajal and Theo Hernandez.
Looking to make it six wins in a row in all competitions, it was perhaps unsurprising that Real had the first chance of the game six minutes in, when Gareth Bale headed Achraf's cross straight at Espanyol goalkeeper Diego Lopez from point blank range.
Lopez was called into action again just before the quarter hour mark, as he was forced to tip the ball over the bar after his own defender Aaron Martin deflected Isco's cross on target; with Raphael Varane heading the resultant corner into the ground and past the post.
Espanyol then went close to opening the scoring themselves after 25 minutes, as Varane's rushed clearance was intercepted by the head of Carlos Sanchez, who subsequently found Gerard Moreno inside the Real penalty area. His attempt, however, was turned round the post by the leg of Keylor Navas.
Minutes later, Moreno did have the ball in the net only to be ruled out for offside. As Madrid failed to clear their lines from a free kick, Sanchez's shot from distance into the bodies in the area was controlled and turned home by Moreno before the linesman's flag cut short the celebrations; with replays showing the decision may have been tighter than first seemed.
Though Espanyol continued to show their intent going forward, Real once again began to threaten in the final stages of the first half. Bale was somewhat unlucky not to be awarded a penalty 40 minutes in, as his low shot from a tight angle cannoned away off the arm of the sliding Victor Sanchez.
It was the Catalan hosts who started the second half the more promising, with a far post volley from Sergio Garcia tipped behind by Keylor Navas, leading to a brace of corners, the second of which was headed onto the Real Madrid bar by Oscar Duarte.
Despite Espanyol's promising start to the second period, Real rallied to apply pressure of their own, without ever really threatening to take the lead. With Mateo Kovacic's effort from range which stung the palms of Lopez the closest the visitors came in the fifteen minutes after the interval.
Kovacic then nearly turned provider, as he laid the ball off to Bale on the edge of area following a driving run through the Espanyol half, but the Welshman's effort was well over.
Having ridden out the spell of pressure from their visitors, Espanyol would once again go close to an opener as the game entered its final 15 minutes.
Garcia made space inside the area to produce a central cross onto the head of Moreno, with his downward header forcing Navas to dive down to his left to leap onto the goal bound effort.
Although Zidane signalled his intent to go for the win, sending on both Karim Benzema and Dani Ceballos in the closing stages, it was Espnayol who snatched a last gasp winner, as Sergio Garcia's cross found Gerard Moreno 12 yards out and the in form striker swept home an emphatic finish to give Espanyol their first victory over Real in 22 attempts.