The focus of this encounter is never sole; there are many edges on which an encounter like this precariously leans... At BeSoccer we have compiled a list of the hottest topics being discussed in the build up to Barcelona versus Real Madrid.
1) Who will be missed the most; Messi or Ronaldo?
It is perhaps the most debated topic in the lead up to this match. Barça have to learn to cope without their biggest star in this first third of the season. More of a long-term issue in Madrid is whether the team will continue to pine for Ronaldo, or whether they will finally step up and perform in the absence of the Portuguese.
'El Clásico' amplifies everything. And so the true test for both teams is which one can react better to losing their great leaders of recent years.
In two matches without Messi, the 'Blaugrana' have made his absence a myth. They defeated both Inter and Sevilla, resuming the leadership of the league table and strengthening their hold in their Champions League group in the process.
A win this Sunday would see the side cope without Messi for almost three whole matches (2,3/4).
On the other hand, Lopetegui has neither found the right man to step into the giant void left by Ronaldo, nor a tactical solution that would render his feats unnecessary. Therefore it is essential that Madrid manage to unclog the blockage in their goal scoring department, and fast.
2) Which manager will leave the stronger; Ernesto Valverde or Julen Lopetegui?
Clearly, there are more eyes focused on the progress of 'Los Blancos' manager than those following the 'Blaugrana' boss. In all literal interpretations of the phrase, Lopetegui is taking charge of Madrid on a match by match basis, with the axe of the President ready to swing in his direction at any moment.
The Basque coach has everything to lose, but also a lot to win; there is no better tonic than beating Barcelona, even more so at the Camp Nou. It would be a vital lifeline earned in the eyes of Florentino Perez.
In contrast the 'Txingurri' is travelling at a more steady pace at the Barça helm after the 4-2 win at Wembley this month.
Valverde's place is more assured in Catalonia, not only for being leader in Spain and in Europe, but also due to the various tactical decisions he has taken which have been influential for Barcelona in recent weeks.
In the last fixture against Inter, he replaced Messi with Rafinha, which proved successful.
Furthermore, in beating Real Madrid, Valverde's side would further secure top spot in La Liga, stretching their lead over 'Los Blancos' to seven points.
A victory would not help Lopetegui catch up in terms of the league standings, but such a result would give him the rhythm to end to this current slump.
3) What impact will the use of VAR produce?
A noticeable shift has taken place in football since the introduction of the video assistant referees. The idea that the referees favor bigger clubs is fast disappearing from the underdog's scripts.
This weekend perhaps presents the biggest test of VAR, with the consequences of any decision being more far-reaching than ever.
Sanchez Martínez of Murcia will officiate the match, and will have Hernández Hernández assisting him from the review room. For the time being, VAR has successfully resolved 90% of incidents called into question so far, but will this good form continue?
Will the officials remain level headed and calm in situations that require the use of VAR? Will they bow to pressure from players asking for the use of the reviewing system?
How will the ability to decide in a matter of seconds affect officials knowing that any faults committed by Barcelona or Madrid carry considerably more weight than any other team?
4) Will there be strange occurrences in the dugouts?
Sometimes it happens that, knowing exactly what is at stake, drives the managers of 'El Clásico' to throw in an extra plot twist.
Disappointments and pressure aside, it remains to be seen if Valverde or Lopetegui opt to throw in a curveball substitution or tactical change in order to turn the tie in their favour.
For Barça, in order to get Dembélé firing, the stick and carrot approach is often deployed. It is unclear if Semedo will return to the team or if Sergi Roberto will continue on the right hand side.
Will he boss keep Rafinha in place of the absent Messi in spite of highlighting the former Inter man's lack of consistency?
Lopetegui faces many dilemmas of his own with regards to the right hand side of his starting XI, even without leaving out Lucas Vazquez.
Odriozola or Nacho? Was Varane rested for the Viktoria Plzen clash, or will his punishment for a poor show against Levante continue? Ceballos, in or out? Will the coach opt for two strikers, or will he back Mariano from the start?
5) Ter Stegen versus Courtois or Keylor Navas?
The nets are often decisive in these encounters, but now the associate factors are neither Messi or Ronaldo. Ter Stegen, on the back of a spectacular performance against Sevilla, seems to have hit peak form once again. However in Madrid,for now rotation is the protagonist.
As anticipated, Thibaut Courtois will be the number 1 goalkeeper this season., although the statistics do not support this decision. And, in spite of Lopetegui announcing that Navas is the Champions League goalkeeper, the truth is that the Costa Rican has produced more saves and better saves for 'Los Blancos' up to this point.
Will the manager dare to deviate from this declaration? Keylor Navas already has many Clásico matches under his belt, and has been decisive for Real in many of them. In contrast Belgian Courtois has yet to prove himself, and has seemed shakey in big moments for Madrid so far this campaign.
6) Will results continue to fluctuate?
If historically home advantage has been a factor, in the last few seasons it has seemed to count for nothing.
Barcelona and Madrid have begun campaigns with good results at home; yet Barcelona have won three of their last four visits to the Bernabéu, and Madrid have gone three consecutive games without defeat at Camp Nou.
7) Will the match earmark Modric as the prime candidate for the Ballon d'Or ?
It is becoming increasingly evident that this year's winner of the Ballon d'Or will come from the trident of Modric, Griezmann and Ronaldo. Encounters like these are fundamental in separating the best from the rest.
The Croatian midfielder has been touted as the favourite for the prize, veen more so after claiming FIFA's 'The Best' and UEFA Player of the Year in recent months. However the crisis in Madrid has somewhat engulfed the diminutive play maker.
There is nothing like having the performance of a lifetime at the Nou Camp and leading a convincing victory. 'El Clásico' is a global event, broadcast on all five continents, and is always a great topic of debate, and even more importantly, Sunday marks two months until 'France Football' announce their winner.
8) Will Luis Suarez be the 'Blaugrana' saviour?
The Uruguayan forward , in the absence of Messi, took a large step forward in terms of responsibility and leadership. He did not score against Inter, but it was certainly not for the want of trying. He has recovered the hunger to drag his side over the line.
He always performs well against Madrid. Yet the season has started in somewhat bleak fashion for Suarez, as he more often than not finds himself assisting his teammates as opposed to scoring himself.
9) Will there be an unexpected star appearance in 'El Clásico'?
Luis Suarez, Benzema, Coutinho, Bale, Ter Stegen, Modric... Many names have already been put on the table to take the fixture by storm. Yet there are many factors at play in this enounter, and so nothing can be totally ruled out.
Will Artur be the spearhead of a 'Culé' triumph? Will Varane return to his best level? Will Odriozola perform like never before on the right hand side? Is it possible that we could be discussing an Arturo Vidal masterclass instead of his emojis? Will Valverde restrict anyone who is keen to flatout attack Madrid? Could Denis Suárez emerge as the vital face for Barcelona?
10) Will Vinicius finally be given a chance?
Week after week, Lopetegui is hounded by the same question: will you try Vinicius? Freed from his ban and also omitted from the Castilla squad list, what seems to be the umpteenth opportunity to gamble on Vinicius, has the moment finally arrived?
Could now at the Camp Nou be the perfect moment to release Vinicius upon La Liga? Could it be interpreted as a final throw of the dice from Lopetegui before Florentino Perez throws in the towel?
Interpretations aside, the energy that the Brazilian possesses is undoubtedly a unique factor, especially in the second half, that could offer different solutions to the faltering 'Los Blancos' attacking line.