Nuno Espirito Santo's men have won four on the spin to move seven points clear of Sevilla in the race to secure a top-four finish.
However, with third place enough to seal an automatic UEFA Champions League place - thus avoiding the play-offs - Valencia will have their sights firmly set on usurping Diego Simeone's side, who are just a point better off.
Valencia have not won on any of their past five visits to the Vicente Calderon and midfielder Enzo Perez knows they face a tough challenge against an Atletico side that has only lost once in the past 33 home league games.
"It'll be a very difficult game against a great team, who are playing in the Champions League and on the up," he told Marca.
"I had the opportunity to work with [Diego] Simeone for six months at Estudiantes, although he has evolved since then.
"His idea is to play intensely and not give the ball away. We know it'll be a game like that, but we'll try to counter that and have a good match.
"Atletico are the champions, ahead of us [in the table] and at home, so they're the favourites.
"They have to please everyone, but we'll try to have a great game and do things in the best way possible in order to achieve a good result."
While Valencia come into the game buoyed by a strong run of results, Atletico have dropped points in recent weeks against Celta Vigo and Sevilla to fall seven points off the pace of leaders Real Madrid.
"We are very eager," said Atletico defender Jesus Gamez. "We tied against a great team such as Sevilla and in a difficult match but, above all, it didn't cut points in the ranking.
"We know that Valencia is closer and it will also be a difficult match, but we have the support of our fans and the team's eagerness for that moment to arrive.
"We're a team with a very united group, especially with the coach. We're training well and all the players are needed at this time. And the union of the group is essential."
Atletico look likely to be without Saul Niguez, who took a blow to his kidneys in the Champions League defeat to Bayer Leverkusen last week.
Valencia, meanwhile, have doubts over Nicolas Otamendi, who picked up a sprain to his left ankle in the 2-0 win over Real Sociedad last time out.
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