Jose Mourinho's nine-year unbeaten home league record as a coach came to an end as his Real Madrid side lost 1-0 to Sporting Gijon at the Bernabeu.
Miguel de las Cuevas scored in the 79th minute to give the visitors a shock Primera Liga win and inflict a first home defeat on Mourinho in 151 games.
The Portuguese coach had overseen 23 home wins this season after going unbeaten at Inter Milan and Chelsea.
His only other home defeat came when Porto lost 3-2 to Beira-Mar in 2002.
The result was also a bitter blow to Real's title hopes, leaving them still five points behind leaders Barcelona but having played a game more.
"Mathematics says the league is not lost but objectively speaking if the gap goes from five to eight points we can say that it's almost impossible," said Mourinho.
"Luck is part of football and our opponent [Gijon] had it all and we had none."
Real defender Sergio Ramos believes his side's hopes of winning La Liga are all but over.
"Being realistic, yes more or less. There are very few points left available," said the Spain international.
"You cannot blame the team in any way as the ball just unfortunately wouldn't go in today. It's very sad to lose when you have so many chances."
Joint La Liga top scorer Cristiano Ronaldo, striker Karim Benzema and full-back Marcelo all missed the game through injury.
And looking ahead to Real's Champions League clash against Tottenham on Tuesday, Mourinho added: "If I had wanted to draw the game 0-0 from the start I would have done so. But a draw was a bad result.
"Against Tottenham on Tuesday, it won't be. If we draw at home, it would not be a drama because we will have the return to play in London."