Atletico, on the verge of regaining the trophy they last won in 1996, head into Sunday's trip to Levante four points clear of Barcelona with three matches remaining and six ahead of city rivals Real Madrid, who have a game in hand.
And, after joining Real in the UEFA Champions League final with 3-1 win at Chelsea on Wednesday, the sky-high mood around the Vicente Calderon could be lifted further with the league title in sight for Diego Simeone's men.
Atletico may potentially be crowned champions with victory over a Levante side mired in mid-table with little to play for, although they will need two shock results to go in their favour if that possibility is to become a reality.
Barca host relegation-threatened Getafe, who have never won at Camp Nou, on Saturday and will be completely eliminated from contention should they succumb to a shock defeat and Atletico overcome Getafe.
That unlikely prospect coming to fruition would leave Atletico with a nervous wait to see if Valencia can obtain a surprise win at Real later on Sunday that would see Simeone's charges clinch the title.
But the chances of Real following up Tuesday's 4-0 (5-0 agg) Champions League semi-final triumph against Bayern Munich by potentially falling nine points adrift of Atletico with a home reverse to Valencia look to be remote.
Real's magnificent victory at the Allianz Arena keeps them in contention to win the European Cup for a 10th time. And they will need no extra motivation to maintain their hopes of the treble with a win over Juan Antonio Pizzi's men.
The battle for the fourth and final Champions League qualification place is also one that may be decided this weekend, with Athletic Bilbao in pole position following their 3-1 victory over nearest challengers Sevilla last Sunday.
Ernesto Valverde's men will seal a place in Europe's premier club competition with three points regardless of Sevilla's result at Villarreal.
Meanwhile, at the other end of the table, Granada will look to move on to 40 points and edge closer towards ensuring top-flight survival by beating a Real Sociedad side hoping to make sure of a UEFA Europa League spot.
Elche visit Malaga with designs on pulling further clear of the bottom three, while Real Valladolid and Almeria each have the chance to pull out of the drop zone against Espanyol and relegated Real Betis respectively.
Elsewhere, Osasuna can boost their prospects of staying up with success against Celta Vigo.
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