Real Madrid's nightmare afternoon was made worse by another injury to Eden Hazard, who was forced off in the second half of their 0-1 defeat to Levante.
Barcelona were beaten 0-1 by Athletic Bilbao at San Mames while Real Madrid lost 3-4 in a seven-goal thriller to Real Sociedad at the Santiago Bernabeu.
Barcelona can cut the gap back to three points by beating Levante at home on Sunday but Atletico Madrid now trail leaders Real Madrid by 13 points.
If Eden Hazard returns against Sevilla in La Liga on January 18 he will have been out for almost eight weeks.
Coach Zinedine Zidane brought on Gareth Bale and Luka Jovic, but Real Madrid failed to find a winner.
Ernesto Valverde has called for unity around Wednesday's El Clasico amid fears the world's most famous football match could be marred by Catalan independence protests.
Real Madrid and Barcelona have rolled through the gears in the lead-up to Christmas, meaning the winner of Wednesday's crunch meeting at Camp Nou will move seven points clear of third place.
Karim Benzema scored a dramatic injury-time equaliser to salvage a 1-1 draw for Real Madrid against Valencia at Mestalla.
After Barcelona, Real Madrid play at home against Athletic Bilbao, to complete a tough week before La Liga's Christmas break.
Eden Hazard could be sidelined for more than a month after suffering a fracture in his ankle while Marcelo might also miss the game against Barcelona, after he sustained a calf strain in training.
Real Madrid face PSG at the Santiago Bernabeu, with Gareth Bale's future in doubt and his standing among the fans perhaps never lower.
Trouble returned to Real Madrid after they endured their first La Liga defeat of the season at newly-promoted Real Mallorca.
Real Madrid are a point ahead of promoted Granada and Atletico Madrid after Diego Simeone's side failed to break down their well-drilled local rivals.
Eden Hazard missed the start to Real Madrid's season with a thigh injury, and has failed to impress in the matches he has played so far
Zinedine Zidane said in July it would be "best for everyone" if Gareth Bale left this summer but it was the Welshman's double that earned Real Madrid a point.
Zinedine Zidane said he believes Gareth Bale will now stay, with the Spanish transfer window closing on September 2.
Zinedine Zidane has made clear that Gareth Bale is not in his plans as he looks to rejuvenate Real Madrid following their miserable season last term.
Harry Kane scored the only goal of the game with a deft finish after pouncing on a disastrous pass by Marcelo.