Goalkeeper Victor Valdes, captain and central defender Carles Puyol and playmaker Xavi are all unavailable for the match against one of only three teams to take points off them this season.
Xavi, who picked up a minor muscle tear in last weekend's 2-1 win at home to Athletic Bilbao, played down the situation, saying they were unlikely to hurt the club's bid for a third successive Spanish league title.
"These are minor injuries, not lengthy ones," he told a news conference on Wednesday, adding he expected to return for the match at Valencia on March 2.
"The injuries are coincidental, caused by stress and too many games - it's normal, just like in any other team."
Mallorca coach Michael Laudrup, a former Danish international who played for both Barca and Real Madrid, masterminded a 1-1 draw at the Nou Camp in early October.
Barca's 2-1 win against Valencia in their next match was the start of a record 16-match winning streak.
As well as the injured trio, Barca will also be without one of their main creative outlets on Saturday.
Right-back Daniel Alves, who has an incredible 14 assists this season in all competitions, is suspended.
However, their prolific attacking trio of World Player of the Year Lionel Messi and Spain pair David Villa and Pedro, who have 77 goals between them in all competitions, is intact.
Real have also been affected by injury ahead of their match at Deportivo La Coruna in Saturday's late kick-off.
The club said on Tuesday midfielder Sami Khedira would be out for two to three weeks after damaging a thigh muscle in Tuesday's 1-1 Champions League draw at Olympique Lyon.
Former Lyon striker Karim Benzema came off the bench to score Real's goal as he continues his bid for a regular starting place under coach Jose Mourinho.
"He's going in the right direction," Mourinho was quoted as saying in Spanish media on Wednesday.
"The whole world knows his potential but his game needs to improve," the Portuguese added.
"He has taken that on board, he's working very hard and he has already improved."
Valencia, 12 points behind Real in third, play at fifth-placed Athletic Bilbao on Sunday.
Villarreal, who dropped below Valencia into fourth after a run of two defeats and a draw, are at Racing Santander, also on Sunday.
