Meanwhile, newly-promoted Huesca head into their clash with last season's Champions League quarter-finalists having already recorded draws away at Villarreal and Valencia.
While much of the media focus has been on the arrival of Luis Suarez over the past week, Atletico Madrid are in a situation where they will want to concentrate on getting early victories on the board.
Although they ultimately finished in third place last season, Diego Simeone required a strong finish to ensure that he continued his long reign at Los Rojiblancos.
Having replaced the inconsistent Alvaro Morata with Suarez, there is a feeling that they can now challenge rivals Real Madrid and Barcelona for the La Liga title.
Suarez was restricted to an outing from the substitutes' bench against Granada on Sunday afternoon, but two goals and an assist came from the Uruguay international's 19-minute appearance.
Simeone must now decide how to manage the fitness of the 33-year-old, aware that keeping the veteran available for selection is key if they want to keep the pressure on the big two.
From Huesca's perspective, a home meeting with Atletico continues their tough start upon their return to the top tier of Spanish football.
Claiming a point against Valencia at the Mestalla represented one of the biggest results in their history, while also ensuring that they remain outside of the relegation zone.
Nevertheless, suffering a 2-0 defeat at home to Cadiz highlighted the size of the task for Michel and his squad in future weeks.
Despite being eager to avoid a heavy defeat on Wednesday, Michel will already have one eye on games against Elche and Real Valladolid as they search for their first victory of the season.
Huesca La Liga form: DLD
Atletico Madrid La Liga form: W
Simeone will almost certainly make a number of changes to his starting lineup, which should include a start for Suarez.
Despite speculation regarding his future, Thomas Lemar may be provided with a chance on one of the flanks.
Huesca possible starting lineup:
Fernandez; Lopez, Pulido, Siovas, Luisinho; Seoane, Mosquera; Garcia, Real, Ferreiro; Okazaki
Atletico Madrid possible starting lineup:
Oblak; Trippier, Savic, Felipe, Lodl; Lemar, Llorente, Partey, Niguez; Felix, Suarez
We say: Huesca 0-4 Atletico Madrid
While Huesca deserve credit for their start to the season, this match may prove to be one step too far. Atletico were in ruthless mood against Granada, and we expect more of the same on Wednesday evening.