Current La Liga holders Barcelona have the advantage if they finish level on points with their title rivals at the end of the season.
If Barcelona end up level with either Atletico Madrid or Real Madrid at the end of the La Liga season, the Catalan club will prevail on the head-to-head rule.
Unlike the Premier League, which is settled on goal difference, La Liga's tie breakers are decided by a straight aggregate scoreline between the two sides, and with just four points separating the top three with six games remaining, the ruling could come into action on May 15.
Real sit four points adrift, and despite beating Barcelona 2-1 in El Clasico earlier this month, their 4-0 defeat earlier in the season has them at a disadvantage.
Atletico, champions in 2013/14, reduced the gap to three at the weekend, but they lost both their league games against Barcelona earlier in the season 2-1.
If Atletico and Real Madrid were to finish level on points, Atletico would prevail having beaten their city rivals at the Bernabeu earlier this year, following a 1-1 draw at the Vicente Calderon last autumn.
The scenario occurred in 2006/07 when David Beckham's Real Madrid won the La Liga title on a head-to-head record against Barcelona, despite having a goal difference of +26 compared to Barca's +45.
None of the top three sides chasing the title this season will be playing each other in the final six games, but Barcelona's form in the last fortnight has opened the door for Real and Atletico.
Luis Enrique's side host Valencia on Sunday in the next round of fixtures, while Real go to Getafe (Saturday) and Atletico host Granada.