Barca lead fourth-placed Madrid by 11 points at the top of the table, albeit Real do have a game in hand.
However, it was at the Santiago Bernabeu that Barca last tasted defeat in August as Real cruised to a 5-1 aggregate win in the Spanish Super Cup.
Here, AFP Sports looks at five keys to deciding who will end the year victorious.
Barca have overcome Neymar’s departure with relative ease thanks to left-back Jordi Alba’s return to form, in large part caused by the Brazilian’s absence on the left side of Barca’s attack.
“I have a lot more room to go forward and in all honesty for me it is much better,” admitted the Spanish international.
Lionel Messi has also benefited with three of Alba’s six assists this season setting up the Argentine.
The Alba-Messi connection also gave Barca a famous 3-2 win as Messi scored with the last kick of the ball at the Bernabeu in April when Neymar was suspended.
Madrid right-back Dani Carvajal has played just five games since September due to a long-term virus and a lack of cover offered by Madrid’s narrow four-man midfield could give Alba plenty of space to exploit.
Madrid’s famed ‘BBC’ front three of Cristiano Ronaldo, Karim Benzema and Gareth Bale have yet to play a single minute of action together this season, largely due to Bale’s injury problems.
However, the Welshman scored on his return to action to help Real win the Club World Cup last week leaving Zinedine Zidane spoilt for choice with his starting line-up.
Zidane is expected to stay loyal to the side that started the Champions League final in May with Bale only featuring from the bench.
Yet, the pace offered by Bale and Marco Asensio, who has scored in his last three matches against Barca, could prove decisive in the second-half.
Between them Ronaldo and Barca’s Luis Suarez had a pitiful return of a combined four goals in La Liga until mid-November as age appeared to be taking hold of both now in their 30s.
However, Ronaldo and Suarez now look like their old selves to add plenty more firepower to a fixture never short on goals.
Ronaldo has eight in his last seven games, including the winner in the Club World Cup final last weekend.
Suarez, meanwhile is now La Liga’s joint third highest scorer thanks to six in his last five league games.
Ernesto Valverde’s version of Barca may lack the same spark as those coached by Pep Guardiola and Luis Enrique over the past decade, but the results are just as good thanks to an exceptionally mean defence backed up by the brilliance of Marc-Andre ter Stegen in goal.
Valverde’s men have kept 17 clean sheets and conceded only eight goals in total on their 24-game unbeaten run.
The real test, though, comes at the Bernabeu, especially with Thomas Vermaelen expected to deputise for the injured Samuel Umtiti at centre-back.
Barca have kept just one clean sheet against Madrid in their last 24 meetings.
Of all the stars on show, Brazilian international duo Casemiro and Paulinho may not be the most pleasing on the eye but both bring a physical edge to the midfield battle that make them vital components to their respective sides.
Casemiro is Madrid’s destroyer who creates the platform for Toni Kroos, Luka Modric and Isco to create.
However, he will have to keep a close eye on his compatriot, whose ability to time his runs into the opposition area has seen him register six goals in 15 La Liga appearances and quickly quieten the critics who questioned his 40 million euro signing from Chinese side Guangzhou Evergrande.
Provided by AFP Sport
The world player of the year received rough treatment as he scored the winner in the Club World Cup final over Brazilians Gremio last weekend, but Ronaldo had insisted he would be fit for the lunchtime visit of league leaders Barca.
Ronaldo didn’t train with the rest of the Madrid squad on Tuesday, Wednesday or Thursday as a precaution.
Madrid will need Ronaldo in the form he has shown of late having scored five goals in his last four games as the European champions look to claw their way back into the title race.
Zinedine Zidane’s men trail Barca by 11 points and are in fourth place also behind Atletico Madrid and Valencia, but they do have a game in hand on their rivals.
— Real Madrid C.F.🇬🇧 (@realmadriden) December 21, 2017
In the above video, Sport360's Brendon Netto covers several talking points ahead of the crucial Clasico.