The champions are on a high after knocking holders Real Madrid out of the King's Cup on Thursday but Simeone said he was wary of a Granada side whose players will be desperate to get their season back on track.
Youth coach Joseba Aguado will take charge of the team for Sunday's game while the club seek a replacement.
"When a coach leaves motivation is higher because more responsibility falls on the players," Simeone told a news conference on Saturday.
"The responsibility passes to the players and they will be excited about the game and imposing their speed in attack," added the Argentine, who led Atletico to their first La Liga title in 18 years last season.
"We have to manipulate the match in a way that plays to our strengths and generate intensity in our play."
Atletico are third with just under half the season played, three points behind second-placed Barcelona and four adrift of leaders Real, who have a game in hand.
Real play at Getafe and Barca are at Deportivo La Coruna on Sunday, before the Catalans host Atletico for a King's Cup quarter-final, first leg on Wednesday.
Simeone said Fernando Torres, who struck twice in Thursday's 2-2 Cup draw at Real that sent Atletico through to the last eight 4-2 on aggregate, would start Sunday's game up front with Croatia forward Mario Mandzukic.
Spain international Torres returned to his boyhood club on loan from AC Milan this month following seven mixed years in England and Italy.
(Reporting by Iain Rogers, editing by Toby Davis)
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