The Argentinian forward damaged a hamstring in Tuesday's 2-2 Champions League draw at Paris Saint-Germain and has been ruled out of the clash at Camp Nou, where Barca will seek to protect their 13-point lead over second-place Real Madrid.
Messi's importance to the Catalan giants extends beyond his goal-scoring exploits.
As well as netting 43 of Barca's 90 goals in La Liga and eight of 17 in the Champions League this season, he has provided a total of 13 assists in the two competitions, second only to Andres Iniesta, who has one more.
The last time Barca lost Messi to injury was in November 2009, when he was out for a week and missed a Champions League Group F game at home to Inter Milan, which Barca won 2-0.
It is still unclear how long he will be sidelined and Barca have not ruled him out of Wednesday's return leg against PSG.
Right-back Daniel Alves, who provided the exquisite pass that sent Messi clear to score on Tuesday, said the Argentine's absence was a chance for other players in the squad to step up.
"The fact that we don't have him is an incentive to prove to everyone that we have enough quality to compete without him and show that we can do it just as well as when he's here," Alves said.
As well as dealing with Messi's absence, coach Tito Vilanova will need to reshuffle his defence for Mallorca's visit, since the injured trio of Carles Puyol, Javier Mascherano and Adriano remain unavailable.
Vilanova, who returned to Spain at the end of last month after cancer treatment in New York, may opt to drop Sergio Busquets or Alex Song back from midfield to partner Gerard Pique, or deploy 22-year-old youth-team product Marc Bartra.
Alves has also played at centre-back in the past and offered his services if required.
"If I remember correctly, I played in that position with Guardiola when we played a back line of three," he said.
"It's easy for me to adapt. If I'm asked to attack, then I attack; if I'm asked to defend, then I defend, and if I'm asked to do both, I do my best."
With Champions League games to negotiate during the week, Barca, Real and Malaga are all playing on Saturday. Real host mid-table Levante, while Malaga can climb above Real Sociedad into fourth.
France: Marseille's Joey Barton in trouble for offensive tweet
Joey Barton has been summoned by the French football federation’s Ethics Committee after the Marseille midfielder called Paris Saint-Germain’s Brazilian defender Thiago Silva an “overweight ladyboy” on Twitter.
"Joey Barton has been summoned by the Ethics Committee and will be heard on April 15,” committee president Laurent Davenas told Reuters by telephone on Thursday.
Barton, who has more than two million followers on the micro-blogging site, has been involved in a spat with Silva this week following disparaging comments the Briton made about some of the PSG player’s international teammates.
PSG threatened action against Barton on Wednesday after the Marseille midfielder likened Silva to a transsexual and called him an “overweight ladyboy” on his Twitter feed. Silva has not responded on Twitter.
Barton’s tweet caused a stir in French media, making the front page of sports daily L’Equipe which asked: “That is British humour?”
Marseille have apologised to Thiago Silva and PSG on behalf of Barton. “Olympique Marseille and Joey Barton wish to apologise to Thiago Silva and his club for the inappropriate comments the English player made on social media in the past 36 hours”, OM said in a statement on their website. “Olympique Marseille officials have asked Joey Barton to end the row between him and the Paris Brazilian defender. The OM midfielder has promised to end right now the publication of any invidious comment against Thiago Silva.”
Barton arrived in France on loan from Queens Park Rangers following a colourful career in England, during which he spent two-and-a-half months in prison for assault during a night out in Liverpool.
At the time of the attack, he was already on bail for attacking former Manchester City teammate Ousmane Dabo, a former France international, and he stubbed out a cigar in the eye of a youth-team player at the club in 2004.
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