Lionel Messi will be out for three weeks after suffering a groin strain as he limped off in Barcelona's 1-1 draw against Atletico Madrid.
The five-time World Player of the Year missed Argentina's World Cup qualifier with Venezuela earlier this month due to the problem and only started Barca's shock 2-1 defeat to Alaves 10 days ago on the bench as coach Luis Enrique bedded him back into action gently.
After an innocuous tussle with Atletico's Diego Godin in the second half of Wednesday night's La Liga clash at the Nou Camp, the 29-year-old went down holding his groin, and was eventually brought off looking distraught.
Barcelona confirmed on their Twitter account after the game that the Argentine will be out for three weeks with a groin strain in his right leg.
"To lose Messi means that football loses," Enrique said after the draw. "With Messi we are stronger, but we will continue being strong."
Messi's absence had an immediate impact as Angel Correa scored for Atletico just a minute after his international teammate went off to level the scores at 1-1.
The Argentine's replacement Arda Turan had barely taken up his position when Atletico levelled as Correa coolly slotted home after Javier Mascherano's slip offered him a clear path to goal.
The injury means Messi will likely miss games against Sporting Gijon (away), Monchengladbach (away), Celta Vigo (away) and Deportivo (home), but should return for the home Champions League clash with Manchester City on October 19.
And Enrique later admitted it would be "difficult to protect" Messi with so many games coming thick and fast for Barca and with Argentina no doubt desperate to have him involved in next month's World Cup qualifiers.
Meanwhile, Enrique said Atletico had been a tough nut for his side to crack.