However, Sevilla make the trip to Camp Nou having not recorded a victory at the home of the Catalan giants since 2010.
Barcelona have enjoyed a strong season in each of La Liga and the Champions League, but Ernesto Valverde's side have work to do if they are to remain in the hunt for the treble.
The Spanish giants needed to overcome a deficit to get the better of Levante earlier this month, and they face the same scenario heading into this week's second leg with a team who have spent the campaign at the top end of the standings.
Valverde made changes for the trip to Seville last Wednesday, but the Barca boss would have expected a better effort from the side that he selected and that may lead to the club's star men being used for the reverse fixture.
Lionel Messi has already completed 90 minutes on four occasions since the short winter break, but Valverde will be tempted to call upon the Argentine maestro with goals coming in each of his last seven outings in all competitions.
The match is being staged at a time when a couple of Barcelona's fringe players are being linked with transfers before the end of the month, but the injury to Ousmane Dembele may highlight to Valverde that he needs to provide more opportunities to either Denis Suarez or Malcom.
Both were only unused substitutes for the weekend's 2-0 victory at Girona, and whoever remains at Camp Nou will be hoping for a show of faith from their manager.
Valverde will not be completely satisfied with his team's most recent performances, but Barcelona do head into this encounter having won each of their last six domestic games at their home ground for the loss of just two goals.
The general expectation is that Barcelona will continue that run against Sevilla, but a more rounded display will be required to secure a place in the last four.
Recent form: WWLWL
Recent form (all competitions): LWWWLW
The disappointment of putting together a return of one win and three defeats from five outings after the winter break had the potential to bring all of Sevilla's previous momentum to a halt, but last week's win could now act as the catalyst for greater things to come.
Losing to Athletic Bilbao twice in quick succession and to Real Madrid at the Bernabeu without scoring a goal was not ideal preparation ahead of a meeting with Barcelona, but Pablo Machin's men rose to the occasion when provided with the ultimate test.
Barcelona had their moments at Ramon Sanchez Pizjuan, but Sevilla were fully deserving of their rare win against their more illustrious opponents and now have something to work with at Camp Nou.
That result was followed up by the 5-0 thrashing of Levante but that win - in some regards - is irrelevant, with Machin needing to put together a whole different gameplan to gain a result against Barcelona.
Sevilla have already travelled to Barcelona this season, and on that occasion the home side were two goals ahead within 12 minutes and eventually went on to register a 4-2 win.
A repeat of that scoreline would be enough for Los Rojiblancos on Wednesday night, but Machin will be aware that his side cannot afford to start so slowly on their second visit to Camp Nou in just over three months.
Nevertheless, Sevilla have not been short of goals this season, with an average of two strikes per game coming from 27 matches in La Liga and the Europa League.
Finding a third goal in this tie would make things significantly easier, but Machin knows that progress will only be achieved if both he and his team can find the right balance with their approach.
Recent form: DWWLW
Recent form (all competitions): WLLLWW
Machin is unlikely to move away from the system he used in the opening leg, with Quincy Promes being used further forward rather than at wing-back like he was at the weekend.
Barcelona possible starting lineup:
Cillessen; Semedo, Pique, Lenglet, Alba; Roberto, Arthur, Vidal; Messi, Boateng, Malcom
Sevilla possible starting lineup:
Soriano; Mercado, Gomez, Kjaer; Navas, Banega, Amadou, Sarabia, Escudero; Promes, Ben Yedder
Head To Head
Sevilla enjoyed their success last week but as you would expect, Barcelona have dominated this fixture in recent years.
The Catalan giants had put together an 11-match unbeaten run before the game in Seville, with nine wins and two draws being recorded since February 2016.
Sevilla have not defeated Barcelona on their travels since a 2-1 triumph in this competition just over nine years ago.
We say: Barcelona 3-1 Sevilla
We expect Barcelona to turn on the style to register a win over Sevilla later this week. However, the visitors possess quality in attack and we believe that one goal may be enough to send Machin's team through on away goals.