Previews: Barca treble quest resumes in Valladolid
Next Wednesday, they host Bayern Munich for the first leg of their Champions League quarter-final, and if they make it all the way to Rome need to be prepared to play 16 games before the end of next month.
"We cannot afford to have one bad week," Barca's Brazilian defender Silvinho said, perhaps aware that the side have only won one in four after international breaks this season.
"People say a particular competition may take it out of us physically, but the problem is we want to get as far as possible in each one," he added. "We are optimistic and working hard to win a treble."
Coach Pep Guardiola could have defender Carles Puyol and midfielders Andres Iniesta and Yaya Toure back in contention after injury against their ninth-placed hosts.
Champions Real Madrid have few such distractions with only the league left to play for, and they are pushing hard with 12 wins from their last 13 outings.
On Saturday, they visit an eighth-placed Malaga side still licking their wounds from a 6-0 mauling away to Barcelona two weeks ago.
"It will be a great game for the fans and everyone is determined that we make up for the poor performance in the Nou Camp," Malaga defender Weligton said.
Third-placed Sevilla have an Andalucian derby away to Recreativo Huelva on Saturday, and fourth-placed Villarreal visit Almeria at the same time.
At the foot of the table, time is running out for bottom club Espanyol, who are eight points from safety. They host Deportivo Coruna on Sunday.
The team above them, Numancia, are four points short of safety and Saturday's hosts Real Betis. Betis coach Paco Chaparro has been under pressure from fans after a run of six matches without a win.
"Chaparro will be with us until the end of the season. Fans should regard it as a new beginning for him, like on the two previous occasions when he stepped in to save us," Betis president Pepe Leon said.