When Real were sat at the top of the standings several weeks ago, Zinedine Zidane still found himself coming in for criticism with his side less than convincing in some of their victories.
With just one win coming from their last five in all competitions, which includes defeats in the Copa del Rey and Champions League, Zidane has come under further scrutiny from a demanding fanbase.
Although a win over their great rivals will change the mood at the Bernabeu, a second successive loss in La Liga will leave Barcelona five points clear with just 12 matches remaining.
When taking the manner of their setback against Man City into consideration, Zidane will feel that Sunday's showdown has come at the perfect time for his players to prove their worth.
Karim Benzema has 18 goals to his name for the season, but the experienced Frenchman has now gone five games without finding the back of the net.
The fact that Real have struggled since the 32-year-old's drop-off in the final third highlights their reliance on the frontman, putting the onus on one of his teammates to step up with Eden Hazard seemingly out until the summer through injury.
While Gareth Bale has found himself in and out of the team in recent months, you have to go back to October 5 for the last time that the Wales international contributed a goal or assist for the Spanish giants.
Having only featured as a substitute against Man City, it may take a big occasion such as the one on Sunday to act as the catalyst for the 30-year-old to rediscover his touch in a Los Blancos shirt.
However, after an indifferent start to life at Camp Nou, Setien has witnessed Barca record three successive wins in La Liga, a streak which has taken the club back into first place.
Their unbeaten run was extended on Tuesday night with a 1-1 draw away at Napoli in the Champions League last 16, putting the Catalan giants in a position to take advantage in next month's reverse fixture.
There will be those who still have reservations about the former Real Betis man, but the 61-year-old deserves plenty of credit for improving results when having to contend with numerous selection issues.
The pair have chipped in with six of Barcelona's last eight goals, strengthening the argument that the club could miss out of silverware this season should either man join Ousmane Dembele and Luis Suarez in the treatment room.
Despite concerns over a defence which have kept just three clean sheets in 10 matches since Setien's appointment, there is a feeling that Barcelona will always have a chance of victory with their star attacking duo on the pitch.
That said, Griezmann's best work this season has come from the left flank, rather than down the centre in the role he is expected to occupy on Sunday night.
Real Madrid La Liga form: WWWWDL
Real Madrid form (all competitions): WLWDLL
Barcelona La Liga form: WLWWWW
Barcelona form (all competitions): WLWWWD
Despite sustaining an injury during the latter stages against Napoli, Gerard Pique is expected to start for Barcelona on Sunday.
Zidane may take a similar approach with his Real front three, including Isco in the team on the right while having the option to switch the playmaker to a central role.
Real Madrid possible starting lineup:
Courtois; Carvajal, Varane, Ramos, Mendy; Kroos, Casemiro, Valverde; Isco, Benzema, Bale
Barcelona possible starting lineup:
Ter Stegen; Semedo, Pique, Umtiti, Firpo; Arthur, Busquets, De Jong; Vidal, Messi, Griezmann
Head To Head
Barcelona head into the next staging of El Clasico having put together a seven-match unbeaten streak against their fierce rivals in La Liga.
Although Real recently had success against Barca in the Supercopa de Espana, prevailing in those matches at the start of the 2017-18 campaign represent their sole victories in recent games.
Madrid have not defeated Barcelona in a home La Liga fixture since a 3-1 win back in October 2014.
We say: Real Madrid 1-2 Barcelona
Although Real are yet to suffer a home league defeat this season, Barcelona will be confident of ending that streak on Sunday. The Catalan giants will have concerns about restricting Los Blancos at one end, but we feel that Messi and co will deliver in the final third.