The two teams locked horns in the final of last season's Copa del Rey, with Barcelona running out 5-0 winners as the Catalan giants landed the trophy for the 30th time.
Sevilla have enjoyed a productive season to date, having booked their spot in the latter stages of the Europa League in addition to performing impressively in Spain's top flight.
The loss to Madrid was actually their third straight defeat in all competitions, while they have not been victorious in the league since the start of the year, which will be a concern to head coach Pablo Machin.
As mentioned, Sevilla reached the final of last season's Copa del Rey, while they have won this competition on five previous occasions, the last of which came in 2010.
Machin's team overcame Villanovense in the round of 32 to set up a last-16 clash with Athletic Bilbao, and despite losing the second leg 1-0 on home soil, they progressed to the quarter-finals 3-2 on aggregate.
The nature of the Copa del Rey and its two-legged affairs mean that it is an extremely busy period of the season for Sevilla, who will be in Europa League knockout-round action against Lazio next month.
Wednesday will bring the first meeting between Sevilla and Barcelona at the Estadio Ramon this season, but the Catalan giants recorded a 4-2 victory when they locked horns at Camp Nou in La Liga back in October.
Sevilla's form in 2019 has been disappointing when considering how they performed in the first half of the season, but a win over Barcelona on Wednesday night would leave the fans dreaming of Copa del Rey success.
Recent form: WLDWWL
Recent form (all competitions): DDWLLL
As mentioned, Barcelona landed their 30th Copa del Rey crown last season and have been utterly dominant in this competition in recent years. Indeed, they have lifted the trophy in each of the last four campaigns and have been present in all but one of the last eight finals, which is some record.
Ernesto Valverde's side had no problems overcoming Cultural Leonesa in the last round, ultimately running out 5-1 aggregate winners to advance to the last-16 stage of the competition once again.
Levante provided some good competition in the round of 32, but a 3-0 home victory in the second leg saw Barcelona progress to the last eight with an aggregate score of 4-2.
Barcelona will enter the match off the back of a 3-1 victory over Leganes on Sunday, which was their seventh straight three points in the league. A total of 46 points has left them top of the table, five clear of second-placed Atletico Madrid on the same number of matches.
Like Sevilla, Barcelona will be in European action next month as they travel to Lyon for the first leg of their Champions League last-16 clash. The treble is certainly on for the Catalan giants, but they will need Lionel Messi to be in full flow if that is to happen.
Messi was named on the bench against Leganes on Sunday, but Barcelona needed the Argentine in the second period to secure all three points and he should return to the starting XI for this match.
The Copa del Rey is third on the list of priorities for Barcelona this season when it comes to the major trophies, but this competition has been very good to the Catalan giants over the years.
Recent form: WWWWLW
Recent form (all competitions): WWLWWW
Munir El Haddadi came off the Sevilla bench for his La Liga debut against Real Madrid and there is every chance that the Spaniard could make the starting XI against his former club this week.
Nolito, however, remains on the sidelines for the home side.
Sevilla possible starting lineup:
Soriano; Mercado, Carrico, Gnagnon; Promes, Vazquez, Mesa, Banega, Vidal; Munir, Ben Yedder
Barcelona possible starting lineup:
Cillessen; Semedo, Murillo, Vermaelen, Alba; Rakitic, Busquets, Vidal; Messi, L Suarez, Coutinho
Head To Head
As mentioned, Barcelona recorded a 4-2 win when the pair met at Camp Nou in La Liga earlier this season.
Their last meeting at the Estadio Ramon was also in the league, with the points being shared in a 2-2 draw in March 2018.
Barcelona also ran out 5-0 winners over Sevilla in the final of last season's Copa del Rey, before recording a 2-1 victory in the Spanish Super Cup back in August.
We say: Sevilla 1-1 Barcelona
We expect the pair to play out a 1-1 draw to leave the tie delicately poised ahead of the return at Camp Nou. Munir to score for Sevilla against his former club and Coutinho to net for the holders.