It has been almost 13 years since Athletic won at Camp Nou and the size of the task they face in ending that run is underlined by Barca's incredible dominance on home soil against all comers.
Since a shock 2-0 reverse to Hercules in September 2010, Barca have lost just twice in 76 home La Liga matches.
Luis Enrique's tenure has started promisingly with six points and two clean sheets from his opening two league games, and the new Barca coach has enjoyed the luxury of having a full squad to work with in training this week.
Full-back Jeremy Mathieu is the only major doubt with an ankle injury, but the international break was otherwise kind to Barca and Ivan Rakitic, Neymar and Rafinha are all fighting fit.
Though it may be a new era at Camp Nou, following a season without a major trophy last term, there are some thing that remain reassuringly familiar.
Lionel Messi scored twice in the opening-day triumph over Elche and the prolific forward can reach another milestone this weekend.
The Argentinian talisman is two goals shy of reaching the 400 mark for club and country.
And the omens are in his favour, too, with the 27-year-old having scored in this fixture for six seasons running.
It was Messi's goal that proved crucial in last season's 2-1 triumph, with Barca having trailed to Aritz Aduriz's strike before Pedro levelled matters.
Athletic, who finished fourth last season and beat Napoli in a play-off to reach the UEFA Champions League, bounced back from their opening-game loss to Malaga by beating Levante 3-0 last time out.
The hosts will sport a changed strip after being granted permission by the league's governing body to wear their 'Senyera' kit.
Barca explained in a statement: "The club's board of directors had requested the change in strip, which features a design based on the Catalan flag, as part of the commemorations to mark the three hundredth anniversary of the September 11 siege of Barcelona in 1714."
