The Liga champions will have to come from behind if they are to stay on course to reach a second successive Champions League final after they were beaten 1-0 at Bayer Leverkusen on Wednesday.
Diego Simeone's men will still be fancied to progress to the quarter-finals, but for the time being they will turn their attention back to their bid to retain the Liga title.
Atleti coasted to a 3-0 home win over Almeria last weekend following a 2-0 lost at Celta Vigo and they can ill afford to drop points this weekend, with city rivals Real Madrid 10 points better off than the champions.
Sevilla were hammered 4-0 by Atleti back in September, with Koke, Saul Niguez, Raul Garcia and Raul Jimenez on target.
Saul is set to miss out this weekend after he suffered breathing difficulties following a challenge from Leverkusen's Kyriakos Papadopoulos and stayed in Germany for treatment.
Koke has been sidelined by a hamstring problem since the derby hammering of Real earlier this month, but the midfielder could return this weekend.
While Atleti will be out to respond to a European defeat, holders Sevilla sealed their place in the UEFA Europa League round of 16 by beating Borussia Monchengladbach 4-2 on aggregate.
Unai Emery's men will face La Liga rivals Villarreal in their next European tie, but beating Atleti at Ramon Sanchez Pizjuan Stadium is their immediate objective.
The Andalusian club have not beaten Atleti in the last 10 meetings between the two sides, a run stretching back to October 2010, but a victory on Saturday will leave them five points behind their opponents.
While Sevilla marching on in Europe, three defeats in their last four Liga games has seen them fall five points behind fourth-placed Valencia.
A 4-3 defeat at Real Sociedad last weekend was their latest setback and if recent performances are anything to go by, winning the Europa League will be their best bet for securing a Champions League spot.
