Diego Simeone's side, who sit three points adrift of leaders Real and one clear of champions Barca in a three-way title duel, play in Seville four hours before the second El Clasico of the season takes place in Madrid.
And with at least one of their title rivals guaranteed to drop points this weekend, victory over rock-bottom Betis would further increase belief that Atletico can upset the odds and claim a first Liga crown since 1996.
The capital club, who have lost just three league games all season, will very much fancy their chances of piling the pressure on Real and Barca by claiming another success, despite Betis' recent upturn in form.
Gabriel Calderon's team have taken five points from their last three outings, but remain nine points adrift of safety with just 10 matches to play.
Betis have been heavily beaten at home by Barca and Real this term, and suffered a 5-0 thumping at the Vicente Calderon back in October.
Diego Costa and David Villa accounted for three of the goals in that reverse fixture and Atleti's lethal strikeforce will be licking their lips at the prospect of playing against the league's second-leakiest defence, with Betis having shipped 56 goals in 28 games this season.
Only Real superstar Cristiano Ronaldo can better Costa's haul of 22 league goals, while Villa has weighed in with 13 to date in his first campaign at the club.
All signs also point towards Atleti keeping a clean sheet this weekend, as they boast the division's strongest defence - having conceded just 21 times in 28 games - while Betis pose the weakest attack, finding the net on only 23 occasions.
Betis can take a small crumb of comfort from the fact all four of their Liga victories this term have come at home, but Simeone will expect to secure a 10th away win of the season before watching matters unfold at the Bernabeu with interest.
