However, Simeone is confident the former Chelsea striker will be fit by the time the two teams resume battle in Europe on May 3.
"The doctors will inform us but I think it won't be possible for him to be ready for Thursday game," Simeone said ahead of Sunday's home league fixture against Real Betis.
"He will be for sure in the return leg, but I think he has no chances to be in the first leg."
While the away game with Arsenal looms on the horizon, Simeone is determined to make sure his squad do not look beyond their next opponents in LaLiga.
The Atleti head coach is wary of an in-form Betis side who sit fifth in the table, singling out defender Marc Bartra - who returned to Spanish football in January after a spell with Borussia Dortmund - for special praise.
"It's always important to do things well. We have to keep on fighting to improve ourselves and try to maintain our position in LaLiga," Simeone told the media.
"We're going to face a team that's playing very well. They've won six straight matches and they've been playing good football. They've improved a lot defensively since Bartra arrived.
"Since then, they've encountered a balance between their offence and defence. This is why they're having one of their best seasons in LaLiga."