Real Madrid were held to a 1-1 draw by Athletic Bilbao after Isco salvaged a point for the visitors with a timely second half strike.
Iker Muniain opened the scoring in the game, prodding home from an Oscar De Marcos cross in the first half.
It was only after the introduction of Isco in the second half when Real kicked into a higher gear. The Spanish midfielder scored just minutes after coming on, ghosting into the box unmarked to head past Unai Simon to make it 1-1.
Key Talking Point
Athletic were the more dangerous of the two sides in the first half, and during the early parts of the second half.
Often they were able to find space in behind Real's defence, which is what happened when De Marcos made a one-two pass with Markel Susaeta before crossing into Muniain to bundle the ball into the back of the net.
Thibaut Courtois could arguably have done better to cut out the cross from De Marcos, but it sneaked past him for Muniain to score. It was a goal Athletic deserved after creating the better chances in the first half compared to Real.
Starting XI: Simon (9), De Marcos (8), Yeray (7), Martinez (7), Yuri (7), R. Garcia (8), D. Garcia (7), Benat (7), Susaeta (7), Williams (6), Munian (7).
Substitutes: Rico (6), Capa (6), San Jose (6).
STAR MAN - Athletic's goalkeeper Unai Simon's performance on Saturday night will have relieved any Athletic fan still worrying about Kepa Arrizabalaga's recent move to Chelsea. Simon is only 21 years old, but he put in a man of the match performance against Real.
In the first half, Simon made a one-handed save from a curling Asensio effort. In the second half, Simon spilled a swerving shot from Gareth Bale's free-kick, but recovered quickly to close down Asensio's shot, who looked sure to score.
WORST PLAYER - It may be harsh to name Inaki Williams as Athletic's worst player of the night. He didn't do an awful lot wrong during the game, but in the same breath, he didn't do an awful lot.
At times he did well to hold up the ball, but playing as the lone striker he often found himself isolated and unable to make much of a difference.
He dragged a shot wide from a fairly tight angle with his effort on goal early in the first half, and that was his best and only chance of the game.
Key Talking Point
The game changed for Real with the introduction of Isco. The Spaniard was subbed on for Luka Modric in the second half, and it was only a few minutes after coming on that he scored Real's equaliser.
Toni Kroos played a great ball over the top of Athletic's defence to find Bale out wide. Bale took the ball under his control, allowed the ball to bounce before swinging in a pin-point cross onto Isco's head.
Starting XI: Courtois (6), Carvajal (6), Ramos (7), Varane (7), Marcelo (8), Kroos (6), Modric (5), Ceballos (5), Bale (6), Benzema (6), Asensio (6)
Substitutes: Casemiro (7), Vazquez (6), Isco (9*)
STAR MAN - Isco replaced Modric around 60 minutes, and it didn't take long for the Spanish midfielder to make the difference for Real. His immediate influence on the game, scoring Real's equaliser after a brilliant cross from Bale, begs the question of why Lopetegui didn't start Isco.
Isco scored against Croatia for Spain during the recent international break, and his impact against Athletic will give Lopetegui something to think about when picking Real's starting eleven for the upcoming Champions League match against Roma.
WORST PLAYER - Real Madrid's number ten Luka Modric was off the pace. He was substituted around the 60 minute mark for Isco, and it was telling that the introduction of Isco provided the energy Real Madrid lacked to break down the Athletic defence.
The midfield three of Kroos, Dani Ceballos, and Modric was defective against Athletic's powerful, pressing midfield. Real's manager Lopetegui changed things at half-time, bringing on Casemiro for Ceballos, but things really came together once Isco was also added, as he was more willing than Modric to add numbers going forward for Real.
Real will be looking to bounce back quickly from this disappointing result which represents early lost points in the title race with Barcelona and city neighbours Atletico Madrid.
Real's next match is against Roma in the Champions League on Wednesday, which is the perfect platform for the reigning champions to hit their stride.