The champions are at home to Real Valladolid and have a one-point lead and the head-to-head advantage over chasing Real Madrid.
At the same time, their arch-rivals visit Malaga, where a victory and a Barca slip up is the only way Real can avoid finishing a second consecutive season without a trophy.
Both Valladolid and Malaga, along with three other sides, are fighting to avoid relegation to the second division.
Last weekend's nervy 3-2 win away to Sevilla saw Barca's players celebrating on the pitch having overcome what had been considered the toughest obstacle left for them, but captain Carles Puyol sounded a note of caution.
"It's a difficult game against a side that is fighting to stay in the league. It won't be a stroll in the park," the Spanish international told reporters. "We'll have to control the anxiety."
Barca have the mixed blessing of playing in front of their own fans at the Nou Camp but face a wily opponent in the shape of former Spain boss Javier Clemente, who has been brought in to try and save Valladolid from relegation.
"Miracles don't exist in football, but surprises do," Clemente told daily Sport.
Guardiola, who played under Clemente with Spain at the World Cup finals in 1994, will be without suspended playmaker Xavi but could have Andres Iniesta back from injury as a replacement.
CALCULATORS AND PENS
A victory for Real in Malaga would see them finish the season with 98 points which is enough to have taken the title every year since the league began. But it will not be enough if Barca also win to move onto 99.
Coach Manuel Pellegrini is having to prepare for the weekend with the local press talking up the possibility of Inter Milan coach Jose Mourinho being brought in as his replacement next season.
"I have a year left on my contract and whether we win or lose (the title) should not condition Madrid's future," the Chilean told reporters.
"You can't say this has been a lesser project when you consider how many points we have achieved."
On Saturday, fourth-placed Sevilla visit Almeria where a victory would secure them the final Champions League qualification slot. They have a one-point advantage over fifth-placed Real Mallorca, who host Espanyol.
At the foot of the table, the three relegation slots will be decided on Sunday with Valladolid, Racing Santander, Malaga and Tenerife tied on 36 points, three ahead of bottom club Xerez.
With the head-to-head rule deciding matters for those who finish level on points, fans will be reaching for their calculators and pens to work out the complicated consequences of each goal as events unfold during the evening.
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