Messi secured himself yet another place in the history books last weekend when he became the first player to score against every other side in the Spanish top flight in successive matches after netting for the 19th consecutive league game.
However, a hamstring injury picked up in Tuesday's Champions League quarter-final first leg draw with Paris St Germain means the Argentina superstar will be absent for the visit of Mallorca.
Losing Messi, whose first-half goal against PSG took his club tally to a remarkable 57 in all competitions this season, is undoubtedly a blow for Barca but defender Dani Alves is viewing his absence as a chance to prove they are no one-man team.
He said: "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."
It is not yet known if Messi will be fit in time for next week's second leg against PSG, but one player who will definitely be missing is Javier Mascherano after he was ruled out for six weeks after suffering knee ligament damage at the Parc des Princes.
Mascherano's injury adds to Barca's defensive headaches with Carles Puyol and Adriano also sidelined while Eric Abidal is yet to feature for the first team since returning from more than a year out having undergone a liver transplant.
Right-back Alves has offered to step in at centre-back if required, saying: "It's easy for me to adapt. I'm ready to do what the manager asks."
Despite their injury problems, Barca should be too strong for second-bottom Mallorca as Tito Vilanova's men look to maintain their 13-point lead over Real Madrid.
Madrid play host to Levante on Saturday in buoyant mood after earning a 3-0 first-leg advantage over Galatasaray in their Champions League quarter-final.
However, with Barca so far clear, Jose Mourinho's men now only look to be playing for second spot in La Liga and they will hope to keep third-placed Atletico Madrid at bay.
Atletico are just a point behind their bitter rivals and will be desperate to finish in the top two for the first time since winning the league and cup double back in 1996.
Coach Diego Simeone, whose side face a derby clash with Getafe on Sunday, said: "I always said that when you're 15th, you want to be 14th. And when you are fourth, you want to be third.
"You always want to advance. And we want to finish as high as possible."
Spain's other Champions League participants Malaga, who drew 0-0 at home with Borussia Dortmund last night, face a big clash this weekend as they go to Real Sociedad.
Sociedad are currently fourth in the table, one point and one place above Malaga.
Elsewhere, last-placed Deportivo La Coruna will hope to boost their survival hopes with a third successive victory when they play fellow strugglers Real Zaragoza, while third-bottom Celta Vigo play Rayo Vallecano, Valencia take on Real Valladolid and Osasuna meet Espanyol.
The 30th round starts on Friday night when Granada host Real Betis while on Monday, Sevilla take on Athletic Bilbao.