Lionel Messi had Barcelona hearts in mouths at the Camp Nou when he went down writhing in agony after falling badly on his right arm - he was substituted but had been generous enough to win the game for his team before he left.
The injury was diagnosed as fracture in the radial bone of his right arm, meaning the Barcelona captain will miss a Champions League match against Inter Milan on Wednesday and next Sunday's Clasico against Real Madrid.
"Psychologically we know that when he is there we are stronger but we can not allow his absence to affect us", Barca centre-back Pique said.
"We have to prepare ourselves, it is clear we are going to notice the loss of Messi but we have players that can cover".
Marcelo finally snapped their long spell without a goal by smashing into the net midway through the second half, scoring the club's first goal in 482 minutes, but despite creating more chances which saw Karim Benzema hit the woodwork and Mariano having a goal ruled out, Real could not find an equaliser.
Local media immediately questioned whether Madrid should fire Lopetegui before the clasico next weekend at Barcelona or give him a chance to try to save his job against the rival.
The Catalans then face three away games in a row against Cultural Leonesa in the Copa del Rey, Rayo Vallecano in La Liga and the return game with Inter.
Messi had also set up Philippe Coutinho for the opener on two minutes. It was his last significant involvement.
The medical staff applied heavy strapping to Messi's right arm but very soon he was replaced by Ousmane Dembele. Sevilla coach Pablo Machin said afterwards. Luis Suarez added the third by converting a second-half penalty kick.
He was still in obvious discomfort as he left the field in the 26th minute.