The league leaders are just a point ahead of arch-rivals Real Madrid, who host struggling Racing Santander, and the build up to next weekend's 'clasico' at the Nou Camp has already begun.
To complicate matters, preparation time is short after the break for internationals and Barca also have to host Inter Milan in the Champions League on Tuesday in a game where defeat could end the defence of their European crown.
"It's vital to win in San Mames to give us confidence," Barca goalkeeper Victor Valdes told a news conference.
"It's always important to hang on to the top spot, not only because the following week we play Real, but because San Mames has always been a tough place for us to visit."
Guardiola will be without the injured Eric Abidal and also have a doubt over Carles Puyol, who picked up a knock while on duty with Spain.
Bilbao, eighth, were hammered 4-1 by Barca in the King's Cup final last May, but the 'Lions' always provide opponents with a tough challenge built around the powerful figure of striker Fernando Llorente.
RESTLESS BERNABEU
Real look to have an easier task at home on Saturday when they host 17th-placed Racing, who have only one league win to their name this season.
After sacking coach Juan Carlos Mandia last week, Racing have yet to appoint a full-time replacement but the visitors could benefit from a restless Bernabeu crowd as Pellegrini's side continue to struggle with inconsistency.
Real were booed from the pitch in their last home game after being knocked out of the King's Cup by third-tier Alcorcon.
Pellegrini received positive news when Cristiano Ronaldo passed a medical on his ankle during the week, and he could make the squad for Saturday after sitting out for over a month.
"It's great news for everyone. His presence is vital and we have missed him," Real sports director Miguel Pardeza told sports daily AS. "We need him."
Third-placed Sevilla are away to promoted Tenerife on Saturday and fourth-placed Valencia, who are unbeaten in 11 matches in all competitions, visit Osasuna on Sunday.
Atletico Madrid, who are in the relegation zone, will try to resurrect their season with a tough away fixture at fifth-placed Deportivo La Coruna on Saturday.
Their preparations have been hindered by new coach Quique Sanchez Flores contracting the H1N1 flu.
