The world's best player suffered a hamstring injury in Tuesday's Champions League draw at Paris St Germain and will definitely miss this weekend's fixture.
His previous 19 league games have yielded 29 goals against every other team in the division, but relegation-threatened Mallorca will be spared his red-hot form. He scored twice against them in the reverse fixture in November, which Barca won 4-2.
Not that it is all good news for the second-bottom side, who are three points from safety.
In the 14 games Barca have played without the Argentina forward over the last three years, they have won 13 and drawn the other.
And Mallorca boss Gregorio Manzano knows the runaway leaders will still pose a threat.
He said: "Barcelona have a great squad. It is an important loss because it's Messi, but no one will deny that those who play are all internationals.
"We shouldn't think about who is missing, we have to think about the 11 players Barcelona will have on the pitch."
Mallorca are 51 points behind their opponents, but Manzano has not ruled out claiming a shock win at the Nou Camp, with the hosts perhaps having one eye on their second leg of their quarter-final with PSG on Wednesday.
"I always think before a game we can win, regardless of the opponents and the circumstances in which we play," Manzano added.
"I think that in football you should not write anything off as lost before playing and with that idea I have tried to make the players understand they have to go to Barcelona to win."
Messi was not Barca's only injury victim from their trip to Paris, with Javier Mascherano also out of Saturday's game.
His absence leaves the hosts with a defensive headache, with Carles Puyol and Adriano also out.
But Davi Alves, who described the game as a chance "to prove to everyone that we have enough quality to compete without Messi", said he was ready to fill in in the centre if needed.
"If I remember correctly, I played in that position with (Pep) Guardiola when we played a back three.
"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. I'm at the disposal of the coaches."