Barcelona have 72 points, two more than Real and Atletico Madrid who play later, but Valdes suffered torn knee ligaments and looks certain to miss the rest iof the season.
"We will not look to bring in a new keeper, we will finish the season with this squad," Barca coach Gerardo Martino told a news conference.
"It is the second injury that Valdes has had. I'm not one to believe in bad luck but in this season so far all that could have happened has happened. It is a heavy blow but this team is used to blows and we will keep going."
The Catalan side were brimming with confidence after their weekend Clasico victory over Real and Neymar scored from close range to put them ahead after six minutes before Lionel Messi slotted home on the half-hour mark.
Neymar latched on to a long ball from Alexis Sanchez and scored his ninth league goal of the season to complete the rout in the second half.
Atletico can return to the top when they take on Granada and Real face a difficult match at Sevilla.
Midfielder Xavi was among players rested for Barca but the changes made little difference as they stroked the ball around and Neymar, badly in need of a boost after a subdued run, knocked in an Alexis cross.
It looked comfortable for Barca as Neymar then hit a shot narrowly wide and Messi was denied by a Yoel Rodriguez save, but at the other end Adriano was booked for handball on the edge of the area and Valdes picked up the injury saving Fabian Orellana's free kick.
Barca pressed forward and it was a trademark link-up between Andres Iniesta and Messi that led to the Argentine knocking the ball past the keeper for their second.
Despite dropping their level after the break and reserve keeper Jose Manuel Pinto being forced into a double save from Augusto Fernandez and Santi Mina, Barca extended their lead through Neymar.
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