Sevilla coach Pablo Machin said a two-goal cushion from their side's Copa del Rey quarter-final first leg against Barcelona could prove "handy".
Pablo Sarabia and Wissam Ben Yedder scored second-half goals in the win.
Midfielder Sarabia gave Sevilla a deserved lead just before the hour and French striker Ben Yedder struck a crucial second with 14 minutes left.
Machin was quoted on the Sevilla website saying it was a shame the victory did not result in three points, adding: "Keeping a clean sheet was extra important tonight, it's hard to keep one against Barca and it puts us in a good position for the second leg."
He said: "Hopefully it is not bread for today and hunger for tomorrow.
"It is the best rival we could face so that the victory was comforting.
"It was demanding, but overall we generated more."
Barca boss Ernesto Valverde handed Kevin-Prince Boateng his debut following his surprise loan move from Italian side Sassuolo on Monday and made six other changes.
Lionel Messi, Luis Suarez, Ousmane Dembele and Philippe Coutinho were among those rested by Valverde, but his side still dominated early possession.
Neither side created a clear-cut chance until Sevilla defender Simon Kjaer's mistimed header from Sarabia's cross flew well wide following a set piece in the 21st minute.
Sevilla, who made four changes from the starting line-up in Saturday's 2-0 defeat at Real Madrid, wanted a penalty four minutes later.
Barcelona midfielder Arturo Vidal appeared to divert a cross with his shoulder, but referee Carlos del Cerro Grande waved away their appeals after consulting with the video assistant.
Sevilla went close again 10 minutes later as Sarabia fired just off target after combining with Ben Yedder on the edge of the box.
Ben Yedder was next to threaten for the home side, but his shot after a fine solo run curled wide, while Malcom spurned Barca's best chance of the half.
The Brazilian raced on to a through ball and skipped round goalkeeper Juan Soriano but then fired wide from a tight angle.
Sevilla were denied the breakthrough shortly before half-time when Jasper Cillessen raced off his goalline to block Ben Yedder's effort.
The second period began in scrappy fashion before Sevilla carved out another chance, but midfielder Ibrahim Amadou got the ball stuck beneath his feet after a cut-back into the penalty area.
Sevilla then got the goal they deserved in the 58th minute. Quincy Promes delivered the cross and Sarabia fired beyond Cillessen into the bottom corner.
Sergio Escudero smashed a shot over the crossbar as Sevilla chased a second before Suarez and Coutinho both stepped off the bench.
Coutinho fired over shortly after and Barca enjoyed their best spell of the match, but Sevilla struck again in the 76th minute, this time against the run of play.
Andre Silva prompted a swift counter-attack and when Ever Banega's shot was deflected into Ben Yedder's path, the striker tapped calmly home.
Barca hogged possession again in the closing stages but created few openings and with new signing Boateng having no impact up front, Sevilla held on to their two-goal advantage.