Leader Real Madrid will look to bounce back from the El Clasico humiliation as it travels to Celta Vigo on Saturday.
A trip to Celta might once have been seen as a chance to rest and reset but the Clasico capitulation has raised the stakes ahead of next week's Champions League first leg against Chelsea.
Madrid is nine points clear at the top of La Liga, which should still be more than enough to hold off a resurgent Barca and Sevilla to win the Spanish title.
But Barcelona's 4-0 victory at the Santiago Bernabeu before the international break has left the door just slightly ajar, with Barca hoping its thumping win can prompt an unexpected collapse from its archrival.
"If there is the slightest option to take advantage, we will go for it," Sergio Busquets said.
Madrid will erase the doubts by prevailing at Balaidos while another slip would create a sense of crisis, especially if Barcelona cranks up the pressure further by winning a tough game at home to Sevilla on Sunday night.
Carlo Ancelotti has been isolating at home this week after testing positive for COVID-19 and it remains to be seen if the Italian is able to take his place on the bench this weekend.
Ancelotti's symptoms are light and Madrid is confident he will return in time for the first leg at Stamford Bridge.
There are also question marks around the fitness of Karim Benzema, whose absence proved hugely significant against Barcelona, not least because Ancelotti caused havoc in his attempts to replace him. If Benzema is not deemed ready, Celta's chances will be considerably enhanced.
Real Madrid's performance on Saturday will also inform the build-up to its meeting with Chelsea on Wednesday when it will need to be at its most assured against Thomas Tuchel's reigning European champion.
Ancelotti might have circled the visit to Vigo as a chance to ease key players back in after some lengthy outings for their national teams but there is less margin now for error, at least psychologically, after the Barca loss.
"I am very sorry for the defeat, I am very sad but I keep it in perspective, which is that we have a nine-point lead in the league and we're in the quarter-finals of the Champions League," Ancelotti said.
The onus is also on Barcelona to back up its Clasico demolition by beating Sevilla if it is to retain any hopes of making Madrid feel uncomfortable.
More likely is victory at Camp Nou will accelerate Barca's pursuit of second, with Sevilla only three points in front, having played one game more.
Xavi Hernandez's side is the form team in the division, unbeaten in the league since December and with five victories from its last five matches.
Concerns over Champions League qualification are a distant memory and it is not inconceivable the Catalans achieve both routes to Europe's premier tournament, by finishing in the top four and then winning the Europa League, where it is surely now the favorite.
Barcelona would be top of the table if La Liga began in January while Sevilla would be fifth, its own hopes of a title challenge undone by a series of draws in recent weeks.
Seven draws in its last nine games have allowed Real Madrid to pull away and while a top-four place should be secure for Sevilla, Barca and Atletico Madrid could yet finish second and third if the downturn continues.
Atletico, now four points ahead of fifth-placed Real Betis, plays at home to Alaves on Saturday, hoping to continue its own revival ahead of Tuesday's first leg against Manchester City. Betis hosts Osasuna on Sunday.
