As well as being a Clasico of firsts, Sunday’s showdown could also be Julen Lopetegui’s Real Madrid curtain call.
The clash at Camp Nou is not only the first Clasico without Lionel Messi and Cristiano Ronaldo since 2007 but also the first to incorporate VAR.
The 2-2 draw in May was the final straw as far as VAR was concerned, and the suspense of reviews should give the encounter an added edge.
Barca remain without Lionel Messi, Samuel Umtiti and Thomas Vermaelen, so Clement Lenglet should continue alongside Gerard Pique in central defence.
Rafinha replaced Messi on the right wing against Inter midweek, opening the scoring in a 2-0 victory, but Clasico favourite Sergi Roberto is likely to come in.
Madrid, meanwhile, have gone four Liga games without a win and came close to going their longest without a goal in 116 years of existence.
That has left Lopetegui hanging by a threat at the helm, and a defeat would surely result in his dismissal.
Los Blancos have problems in defence, with Jesus Vallejo joining Dani Carvajal on the treatment table, so Nacho Fernandez should move out to the right.
Lopetegui is also likely to adopt a 4-4-2 diamond, regularly used by predecessor Zinedine Zidane, with Isco playing just off Gareth Bale and Karim Benzema in attack.
Finally, teenage striker Vinicius Junior is called up after his one-match ban for two yellow cards while playing for Madrid Castilla was overturned.
Los Merengues have gone five Clasicos without a win, their last victory coming in April 2016, but the Catalans haven’t beaten their arch-rivals on home soil for three years.
This will be referee Jose Maria Sanchez Martinez’s second Clasico after he oversaw the Blaugrana’s 3-0 win at the Santiago Bernabeu last December.
The match kicks off at 15:15 GMT/16:15 local time – and you can watch it LIVE on Eleven Sports in the UK & Ireland or follow it with our liveblog!
Barcelona (probable): Ter Stegen; Semedo, Pique, Lenglet, Alba; Rakitic, Busquets, Arthur. Sergi Roberto, Suarez, Coutinho
Injuries/suspensions: Umtiti, Messi, Vermaelen (I)
Real Madrid (probable): Courtois; Nacho, Varane, Ramos, Marcelo; Modric, Casemiro, Kroos; Isco; Bale, Benzema
Injuries/suspensions: Vallejo, Carvajal (I)
Referee: Sanchez Martinez
Form guide: Barca – 2nd (W D D L D) Madrid – 8th (L L D L W)
Previous meeting: Barca 2-2 Madrid
Venue: Camp Nou
Kick-off time: 15:15 GMT/16:15 local time