Real Madrid fell to a 2-0 defeat at Real Sociedad on Tuesday, leaving the champions 14 points behind LaLiga leaders Barcelona with five games remaining.
Former Madrid winger Takefusa Kubo and Ander Barrenetxea netted for the hosts, who tightened their grip on the fourth spot and Champions League qualification.
Madrid defender Dani Carvajal was sent off after an hour for a second yellow card to make matters worse for Los Blancos.
Barcelona beat Osasuna 1-0 earlier Tuesday to expand the gap on Madrid and Carlo Ancelotti's side could not respond.
The Italian played a makeshift side because of injuries and suspensions, and he also left striker Karim Benzema behind in the Madrid capital ahead of Saturday's Copa del Rey final clash with Osasuna.
Alex Remiro denied Madrid defender Eder Militao in the opening stages while Martin Zubimendi struck the crossbar at the other end from close range.
Kubo struck at the start of the second half for the hosts after Militao gave the ball away in a dangerous area.
Carvajal was dismissed for a foul on Real Sociedad forward Mikel Oyarzabal, giving Madrid an uphill struggle.
Madrid goalkeeper Thibaut Courtois did well to parry a deflected Barrenetxea strike, but he could not keep out the forward's next effort, surprising the Belgian at his near post.
Los Blancos' defeat means Barcelona just need two more points to clinch their first title since 2019, provided Madrid win their remaining matches.