Barcelona will take a 1-0 advantage into the second leg of the last-32 tie, with Clement Lenglet scoring the only goal of the first leg at the end of October.
Barcelona landed their 30th Copa del Rey crown last season, and they have been utterly dominant in this competition in recent years. Indeed, the Catalan giants have lifted the trophy in each of the last four seasons and have been present in all but one of the last eight finals, which is some record.
Barcelona have beaten Athletic Bilbao, Sevilla (twice) and Alaves in the last four finals, with their last defeat occurring in the 2014 final against Real Madrid. It has almost been the go-to competition for the Catalan giants in recent years, but they will be desperate to land yet another crown.
Ernesto Valverde's side were far from convincing in the first leg at the end of October though, needing a late Lenglet header to secure an advantage against the 10-man hosts. It will be a completely different match on Wednesday night, however, and would be an incredible shock if they did not advance.
Barcelona will enter the match off the back of a 2-0 win over Villarreal on Sunday night, which was a result that saw them return to the top of La Liga. They also beat PSV Eindhoven in the Champions League last week to secure first position in the group.
In terms of what is ahead for Valverde's team, they have the small matter of the Catalan derby against Espanyol this weekend, before finishing their Champions League group campaign at home to Tottenham Hotspur next week. It is not a huge game for Barcelona, but it is for the Premier League outfit as they bid to beat Inter Milan to second spot in the group.
The year then ends with league games against Levante and Celta Vigo, with the winter break in Spain kicking in after their clash with Celta on December 22. Five matches from Wednesday night, and the Barcelona supporters will be expecting five wins to finish a successful 2018 in style.
Recent form: LWWWWW
Recent form (all competitions): WDLDWW
Leonesa will be bidding to reach the last-16 stage of the Copa del Rey for the first time since the 1959-60 campaign when they travel to Barcelona, and they will have to pull off one of the biggest shocks of all time for that to occur.
La Cultu, who are based in Leon, have previously played at the top level of Spanish football, but their only La Liga season came back in 1955-56. They played in the Segunda Division last term, but ended in 19th position to drop down to the Segunda B, which is the third tier of Spanish football.
Unlike Barcelona, Leonesa's Copa del Rey journey for this season started back in September. Indeed, they overcame Navalcarnero, Fuenlabrada and Lorca in three ties to earn the right to take on the Spanish champions in a two-legged affair.
Leonesa gave a very good account of themselves in the first leg at the end of October but will need a miracle to progress past Barcelona, despite the fact that they are just 1-0 behind from the leg of their last-32 tie.
Leonesa are also not in the best of form. Indeed, Victor Cea's side suffered a 2-0 defeat at Salmantino in the league at the weekend, and are actually without a league victory since they lost to Barcelona in the Copa del Rey in October.
Four draws from their last five matches has left them in fifth position in Group 1 of the Segunda B, three points off fourth-placed Real Madrid Castilla. Leonesa are just six points off the top of the table though, and would draw confidence from a positive performance at Camp Nou on Wednesday night.
Recent form: WLWWWL
Recent form (all competitions): LDDDDL
Carles Alena came off the bench to score against Villarreal and will start, and the 20-year-old is expected to be joined in midfield by Denis Suarez, who is in desperate need of some first-team action.
As for Leonesa, head coach Cea has no fresh injury concerns from the team that suffered a 2-0 defeat at Salmantino in the league on Sunday afternoon.
Barcelona possible starting lineup:
Pena; Semedo, Chumi, Lenglet, Miranda; D Suarez, Alena, Vidal; Malcom, Munir, Dembele
Cultural Leonesa possible starting lineup:
Palasti; Saul, Garrido, Romero, Escalante; Beltran, Bernal, Marcos, Ortiz; Santana, Garcia
Head To Head
These two teams also met during the 2009-10 season in the Copa del Rey. Barcelona recorded a 2-0 victory in the away leg during that particular year before running out 5-0 winners in the return match at Camp Nou.
We say: Barcelona 4-0 Leonesa
Leonesa could take a bit of a hiding at Camp Nou despite their positive performance in the first leg. It will not be a full-strength Barcelona, but the home side should still have far too much on the night.