Mascherano was sent off in last weekend's 5-4 win at Deportivo Coruna and although the club have appealed the Argentine's dismissal, the Spanish federation is unlikely to exonerate him.
Mascherano would join injured Spain pair Carles Puyol and Gerard Pique on the sidelines, while Brazil right-back Dani Alves has not played since being forced off in this month's 2-2 'Clasico' draw at home to Real Madrid.
Midfielders Alex Song and Sergio Busquets and full-back Adriano can fill in at centre back and 21-year-old academy graduate Marc Bartra performed solidly there in Tuesday's 2-1 comeback win at home to Celtic in the Champions League.
Barca playmaker Andres Iniesta netted his first goal of the campaign to make it 1-1 against Celtic and his remarkable record of never losing a match when he scores was preserved.
The Spain international, scorer of the winning goal in the 2010 World Cup final, has 42 goals for his club in the same number of games and Barca have won 37 of those and drawn five.
Third-placed Malaga are also on a high after European success following their memorable 1-0 win at home to seven-times winners AC Milan in Champions League Group C on Wednesday, in what was probably the biggest game in the club's history.
Qatar-owned Malaga, who play at struggling Espanyol on Saturday, have lost only once in 13 games this term in all competitions despite cashflow problems over the summer that led to the departure of some of their best players and delays in wage payments.
"We haven't had it easy and this has made the group even stronger in chasing a goal that through performance on the pitch you can solve the club's internal problems," coach Manuel Pellegrini said after the Milan game.
"There is total commitment to what we are doing and this is reflected on the pitch," the Chilean added.
Valencia, down in ninth place, are looking to get their stuttering campaign back on track at Real Betis to help ease pressure on their Argentine coach Mauricio Pellegrino, who replaced Unai Emery at the end of last season.
The players have sowed the seeds of a revival thanks to last weekend's 3-2 comeback win at home to Athletic Bilbao and Tuesday's 3-0 Champions League win at BATE Borisov, when captain Roberto Soldado scored a hat-trick.
Bilbao's season, meanwhile, is in danger of unravelling after they followed up the defeat in Valencia with a 2-1 Europa League reverse at Olympique Lyon.
Coached by another Argentine, Marcelo Bielsa, the Basque club, who reached the Europa League and Copa del Rey finals last season, are down in 17th place after losing four of their opening eight domestic league games.