The Atletico Madrid boss is anticipating a difficult contest in the Copa del Rey, a competition he is keen to succeed in again, after drawing the first leg 1-1
Atletico go into the game with the tie finely poised following a 1-1 first-leg draw, although Atleti, who sit second in La Liga, will be favourites to progress to the quarter-finals in front of their home fans.
An injury-time strike from Helder Postiga earned a draw for Valencia in the first leg at the Mestalla and although Simeone's side have an all important away goal, the Argentine does not anticipate a comfortable encounter against Juan Antonio Pizzi's men.
"They (Valencia) need to make their mark," Simeone said. "I imagine a game where they will try to play as they did in the closing stages in Valencia, their last minutes were very good.
"We will adapt to gameplay situations that we have seen because they have a great squad and it will be a difficult match with a 50 per cent chance for each side."
Los Colchoneros are level on points with Barcelona at the summit of La Liga and have a Champions League round-of-16 tie with Milan to look forward to next month.
Still, Simeone insists the Copa del Rey holders are taking the competition seriously.
"The Copa del Rey is a competition that has given us many joys," he added. "And we are going to respect it.
"We have that feature, we can play well or badly, win, lose or draw, but our intentions will be the best."