Atletico head into Saturday's clash on the back of three successive defeats, going down twice to bitter rivals Real Madrid in the Copa del Rey semi-finals either side of a shock league loss to Almeria.
That is the Rojiblancos' worst run of results in over three years and, as well as seeing their cup defence come to an end, also saw them surrender top spot in the Primera Division.
Simeone's men are still in a great situation in La Liga, sitting level on 57 points with top two Barcelona and Real, but the former Argentina international knows it is important they react to their recent disappointments in a positive way.
He said: "It is a good chance to show how this team is, we need to have a good game.
"We'll see in what way we can defeat a team who will be coming here highly motivated. Every team in the second half of the season is looking to pick up points."
Despite that warning against a possible upset, Atletico, who play AC Milan in the Champions League last 16 next week, will be overwhelming favourites to beat third-bottom Valladolid at the Vicente Calderon, where they have picked up 32 from a possible 36 points this season.
Unfortunately for them though, Barca and Real will both be expected to pick up victories this weekend as well.
Reigning champions Barca are at home to second-bottom Rayo Vallecano while their Copa del Rey final opponents Real make the short trip to Getafe.
Real have not always found it easy against Getafe, losing five times to their neighbours since their promotion to the top flight a decade ago, but recent form suggests Carlo Ancelotti's men hold all the aces this time.
Whereas Getafe have picked up just two points since November, Real have won 14 of their last 15 matches in all competitions and are unbeaten since October.
Even the absence of Real's suspended superstar Cristiano Ronaldo is not much of a boost for Getafe, with their defender Juan Valera admitting: "Without Cristiano in the last match against Villarreal they scored four goals.
"Real Madrid cannot depend only on one player, and they have many very good players and I don't think his loss will be noticed too much.
"We're aware it's going to be difficult."
This weekend's fixtures begin with Friday night's clash between Elche and Osasuna, while on Saturday - along with the Atletico and Barcelona matches - fifth-placed Villarreal host Celta Vigo and Almeria go to Levante.
The Getafe-Real derby is on Sunday, along with rock-bottom Real Betis' trip to fellow strugglers Granada, while fourth-placed Athletic Bilbao take on Espanyol.
Also on the same day, upwardly-mobile Valencia will aim to replace Sevilla in seventh place when they take on the out-of-form Andalusian side, who have lost their last three.
On Monday night, Malaga take on sixth-placed Real Sociedad.