Tito Vilanova's side make the trip to Real Zaragoza on Sunday with a 13-point buffer between themselves and second-placed Real Madrid.
Lionel Messi came on as a substitute against Paris Saint-Germain in midweek, but it remains to be seen whether he is risked for this match.
With eight games to go the title is all but assured, but for their opponents where they finish in the table is far from certain.
Zaragoza are one place and one point above the bottom three and have not won in the league since beating Athletic Bilbao in December.
However, Alvaro Gonzalez believes his side could get a positive result at La Romareda, pointing to a recent draw against Real Madrid as proof they can compete against the league's best.
"We should be optimistic. It was said it would be very difficult against Real Madrid but we snatched a point - why not against Barcelona?" he said.
Madrid travel to the Basque country to take on an Athletic Bilbao side who come into the game in decent form.
They may have lost 2-1 at Sevilla last time out, but Marcelo Bielsa's side had won three of their previous four and midfielder Ander Iturraspe says his side will not be playing for a point at the San Mames.
"It is a complicated game and we are all in to try and win," he said.
"We will try to press, build up pressure and to maintain our way of playing is the most important thing we can do."
Atletico Madrid are three points off their city rivals and host Granada in a game boss Diego Simeone is desperate to win.
"If we move away from the most important thing, which is to win on Sunday, it will not be good either for the club or for the players and for the fans," he told reporters.
"We have to prepare and play the way we've been doing all year. We have to win on Sunday because it is an important match for our future."
Sunday is an equally important day for fourth-placed Real Sociedad as they travel to Rayo Vallecano in the lunchtime game and try to cement their place in the Champions League places.
"Getting the three points there is going to be difficult because it is a stadium complex and so is the time of 12 noon," said Sociedad winger Antoine Griezmann.
Real Betis and Sevilla kick off the weekend's action on Friday in the Derbi Sevillano, while on Saturday Real Valladolid host Getafe, Levante take on Deportivo and Malaga face Osasuna.
Valencia travel to Espanyol knowing a win is vital if they want to pip Sociedad to a place in the top four.
"We play every game to be in the next edition of the Champions League," said visiting coach Ernesto Valverde.
In the last game of the round, Real Mallorca face Celta Vigo on Monday evening.