The reward for the winner at Valdebebas will be knocking Atletico Madrid out of first place for the first time since December, before it mounted a run that saw it go 10 points clear with a game in hand at the start of February, AFP reported.
But Atletico's recent struggles, combined with a surge in momentum for Madrid and Barca, has seen that advantage evaporate, the question is now whether Diego Simeone's team can recover and regroup to even stay in the race through the final stretch.
Who Atletico has to hold off or, more likely, catch in the last nine games could depend on this weekend's result at the Alfredo di Stefano Stadium, where both clubs will be hoping for the ultimate vindication of recent improvement.
Success for Barcelona would be another significant check-point too in what has been an uplifting few months, the start of a recovery that has run alongside the ongoing uncertainty of what Messi will decide this summer.
Messi's every goal and glance this season has been analyzed for possible indications as to the 33-year-old's thinking but what is clear is how the atmosphere at Barca has changed since he asked to leave for free last August.
Joan Laporta's election as club president, replacing Josep Maria Bartomeu, has brought enthusiasm and, crucially, a sense of direction again, even if the financial problems from the last regime are still very much the problems of the new one.
Messi is not expected to consider offers to renew his contract until the end of the season but Laporta has been pulling hard on the heart-strings.
"Today was the 20th anniversary of a boy named Leo Messi who debuted in the youth teams of Barca," Laporta said in his victory speech last month.
"To see Leo come to vote, the best player in world soccer, with his son for me, is an example of what we've said, that Leo loves Barca and how we are all one big family."
Nurturing young talents
More persuasive might be what Messi has seen and felt on the pitch, witnessing a team that was broken a year ago gradually piece itself back together under Koeman.
Koeman has trusted the club's youngsters and Messi has nurtured them. Pedri, Ronald Araujo, Sergino Dest, Oscar Mingueza and Ilaix Moriba have flourished.
Mingueza, Ilaix, Trincao and Dest have all scored their first La Liga goals, all of them assisted by Messi.
And Messi has thrived too, reclaiming his place at the top of the league's scoring charts with 23 goals so far, and 19 goals in 20 games since the turn of the year.
It may not be enough, given Barcelona was also convincingly beaten by Paris Saint-Germain in the last-16 of the Champions League, the competition Messi centers round more than anything else.
Beating Athletic Bilbao in the final of the Copa del Rey or even Real Madrid and Atletico to the title in La Liga could still see Messi bid farewell.
But if this is to be his last Clasico, 16 years after his first, 44 games that have included 26 goals and two hat-tricks, Messi might see it now as an extra season well spent, the sense of deflation and bitterness gone, and his own place in the revival secure.
"There is only one person who can decide his future and it is him," Koeman said in February. "I would like him to stay for many more years and I just try to make sure he is happy, like he is at the moment."
Whatever the result, Atletico will have the chance to go back to the top of the table on Sunday when it plays Real Betis.