Despite notching a record 96 points, Barcelona must defeat Valladolid at home on Sunday to retain their La Liga title and leave rivals Real Madrid empty-handed as an epic title race reaches its conclusion.
Going into the final day of the season, Real are just a point behind and preying Barca slip-up against troubled Valladolid.
Madrid are at Malaga, another team fighting for survival, knowing they need to win and hope Valladolid take points from the champions.
"It is the most demanding league (campaign) I can remember," said Barcelona captain Carles Puyol. "The table speaks for itself finishing with 99 points is an incredible amount."
"There are two teams that have been above the rest in recent years and Barcelona have certainly played the better football in recent years."
Barcelona have the comfort of knowing their destiny is in their own hands but anything but a win could see them lose the title on the final day of the season.
Real must win to stand any chance of becoming champions as Barcelona would win the title due to their superior head-to-head record if the sides finished level on points.
It is a nervy moment for coach Pep Guardiola who comes up against Javier Clemente once his national coach with Spain and now Valladolid manager.
Valladolid are one of four teams on 36 points that could go down and are only in with a shout of survival after one defeat from seven matches under Clemente.
Guardiola must do without suspended playmaker Xavi and full back Maxwell but can call on Lionel Messi who is set to land the Pichichi crown for the league's top-scorer with his 32 goals, five better than Real Madrid's Gonzalo Higuain.
Malaga are third from bottom but level on points with Racing Santander and Valladolid above them.
"It is difficult to win the league but anything can happen in football," said Real superstar Cristiano Ronaldo.
"We have to win in Malaga and see what happens in Barcelona."
Guti, 33, is poised to play his final game at Malaga ending his 15-year association with Real before an expected summer move to Galatasary.
Elsewhere there are Champions League and Europa League duels and slip-ups on final day could cost teams millions of euros.
Sevilla hold fourth place and the final Champions League qualifying spot but can't afford to drop points against Almeria on Saturday with Real Mallorca just a point behind.
Mallorca are at home to Espanyol aiming for a 15th home win knowing a draw would not do even if Sevilla lost.
Getafe are clinging to sixth and the final Europa League spot with Villarreal level on 55 points.
Getafe travel to city rivals Atletico Madrid who defeated Fulham on Wednesday to win the Europa League final for their first trophy since 1996.
Villarreal will hope Atletico, who have nothing to play for, put the effort in against Getafe and fulfil their end of the bargain by winning away at Real Zaragoza.
There is everything to play for at the bottom with no team relegated as five sides battle to stay in the top flight.
Bottom side Xerez are three points from safety and need to win at Osasuna and hope the four other teams in trouble all lose to pull off the great escape.
Racing Santander, Malaga, Valladolid and Tenerife are all on 36 points.
Malaga and Valladolid have the toughest tasks against Real Madrid and Barcelona giving Racing and Tenerife more hope of staying up as they play against teams with nothing to play for.
Racing are at home to Sporting Gijon while promoted Tenerife travel to Valencia, who have already sealed third place, on Sunday.
Bilbao v Deportivo La Coruna (1700 GMT), Atletico Madrid v Getafe (1900 GMT), Real Zaragoza v Villarreal (1900 GMT), Real Mallorca v Espanyol (2100 GMT), Almeria v Sevilla (2100 GMT)
all at 1800 GMT
Racing Santander v Sporting Gijon, Barcelona v Valladolid, Valencia v Tenerife, Osasuna v Xerez, Malaga v Real Madrid