The Liga clash at the Mestalla will be the Spanish champions' fifth match in the space of 15 days.
Atleti started that run with a 2-2 draw with Celta Vigo, but followed up with three straight wins - including Wednesday's 1-0 success over Serie A champions Juventus in the UEFA Champions League.
This weekend's match with second-placed Valencia represents a challenge to the in-form capital club, who are level on points with their opponents, but head coach Simeone will not allow fatigue to be used as an excuse should Atleti fall short.
Asked if the fixture pile-up would be troublesome, Simeone replied: "No, we are all right.
"We can't do anything about the schedule. All we can do is perform well [against Valencia] as it's an important match and that's what we expect.
"We'll try our best versus a rival with a terrific squad and a very good manager. They counter-attack very well and it will take a massive effort from us to win this game."
Atleti's recent form has left them third in the table, but Simeone is taking nothing for granted in Valencia.
"We focus on one match at a time," he added. "It would be too cocky to think we are going to win.
"Valencia are a great team, very fast on the wings and with quality players. They are very difficult and we need to focus just on them."
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