Barca coach Tito Vilanova has already secured a league crown in his first season at the helm, but can ensure a special place in the history books with a win at home to Malaga that would see them match Real Madrid's record points haul from last season.
Standing in his way is Manuel Pellegrini, who has already announced he is leaving Qatari-owned Malaga and on Wednesday said he had a verbal agreement to join Manchester City.
Runners-up Real will also be bidding farewell to their boss Jose Mourinho, widely tipped to be making a return to Chelsea, when they host Osasuna at the Bernabeu in a game with nothing riding on it.
The rest of La Liga's matches all kick-off at 19:00 with one place into the Champions League play-offs and three into the Europa League to be decided.
At the foot of the standings, four teams separated by two points are battling to avoid the three tickets into the second division.
Most eyes will be focused on Real Sociedad's trip to play Deportivo La Coruna at the Riazor where the final result affects top and bottom.
One of the season's most entertaining sides Sociedad slipped down to fifth with a thrilling 3-3 draw against Real Madrid last weekend, and lie two points short of their only rival for the last slot in Europe's elite club competition, Valencia.
Sevilla, in ninth, play hosts when former boss Unai Emery could spoil hopes of a much needed financial windfall for fourth-placed Valencia.
Deportivo hold the key to the relegation battle in 17th with 35 points as a win would condemn 18th-placed Celta Vigo (34), 19th-placed Real Zaragoza (34) and basement side Real Mallorca (33) to the drop regardless of their respective results.
TERMINALLY ILL
"We've had three coaches, the club has gone into administration, and we were almost declared terminally ill," Depor's leading scorer Riki, 32, told a news conference.
"If we manage to stay up it will be the most important event of my career, even better than winning promotion last year."
Depor's Galician rivals Celta host Espanyol with 17-year-old goalkeeper Ruben Blanco set make his first start for the club, having debuted last weekend as a substitute after Javi Varas dislocated his elbow.
Reserve keeper Sergio Alvarez is also injured.
"We know what he can do because he has been training with us all season; the squad have complete and absolute confidence in him," Celta midfielder Natxo Insa said of Blanco.
Zaragoza host third-placed Atletico Madrid, who could be without leading scorer Radamel Falcao as he missed training with the club's permission on Wednesday. Spanish media reported he was in Monaco negotiating a move to the principality.
Mallorca are at home to Real Valladolid without Israeli top scorer Tomer Hemed, who tore his Achilles tendon last weekend, and probably with
