Gerardo Martino's side have lost their last three games to leave their hopes of a treble in tatters and pile pressure on the Argentinian.
Last Wednesday's 1-0 reverse at Atletico Madrid sealed a 2-1 aggregate defeat in the UEFA Champions League quarter-finals, with Barca going on to lose 1-0 at Granada last weekend, denting their title hopes.
And Catalan misery was compounded on Wednesday with Gareth Bale's late wondergoal securing a 2-1 scoreline and the Copa del Rey for Real Madrid.
The Granada defeat leaves Barca four points behind Atletico and one behind Real although, with the latter not in action this weekend, a win could heap pressure on Carlo Ancelotti's men as the title race enters its final stages.
Despite Barca's stuttering form, Bilbao boss Ernesto Valverde is expecting a tough test.
He said: "I do not know if it is better or worse for us, but this week now La Liga is the only trophy Barca can win.
"The game is difficult, even if they have lost out on two trophies in a week.
"Maybe now they feel more pressure to break the bad run after losing three consecutive games, something they are not used to. But for us it is just as difficult."
Marc Bartra, who was spectacularly out-paced by Bale for Real's Copa winner, should be available after suffering a hamstring strain of his own.
Carles Puyol (knee) may return, but Gerard Pique's cracked hip rules him out and Sergio Busquets is suspended.
After such a detrimental run of results, Barca will be determined to return to winning ways, but it will not be easy against a Bilbao side who look favourites to pick up La Liga's fourth available Champions League spot.
Valverde's charges currently lie six points clear of Sevilla, their nearest challengers for fourth place, and have lost just three of their previous 21 league outings.
Like Barca, Bilbao have injury worries of their own with Mikel Rico (ankle) and Ibai Gomez (hamstring) both major doubts, but Valverde will be praying for a repeat of the reverse fixture in December, when Iker Muniaian's goal ended a winless run of 20 matches in all competitions against the Catalan giants.
