The Argentinian midfielder hurt his left knee during last weekend's 1-0 triumph at Fiorentina.
Tests done this week on the player ruled out any ligament damage although Ledesma will be sidelined for 10 days with a knee sprain.
Lazio will be hoping Ledesma's absence does not hinder the team this weekend as the Romans looks for their third league win in a row, something the Biancoceleste have failed to achieve this season.
Sunday's triumph in Florence was Lazio's 10th win of the campaign and lifted Edy Reja's side to eighth place.
Lazio are just three points clear of Inter Milan, who hold the last Champions League qualifying spot.
"It was important to give continuity to our win against Sassuolo and we did that against Fiorentina," Reja said. "To have taken three points from Florence should give my players a big boost in confidence.
"We are climbing up in the standings and there's no reason why we cannot fight for a European qualifying spot."
Lazio have lost just twice at the Stadio Olimpico this season and take on an Atalanta side that have not won on the road since October 5.
The Bergamaschi have mustered two points of a possible 27 away from home since then.
Atalanta travel to the Eternal City inspired by last weekend's 2-1 triumph over Chievo that lifted them 10 points clear of the drop zone.
The result in Bergamo halted a three-match winless streak for the Bergamaschi and saw them climb to 13th place.
"We wanted to win at all costs and our efforts were rewarded," Atalanta midfielder Carlos Carmona said. "It's a big win for us as it was against a team that like us, is fighting to avoid the drop.
"Now we must try to give our best against Lazio in Rome and try to start taking points away from home."