Calaio, who is Siena's top scorer with 11 goals, fractured his left fibula during last weekend's 2-0 triumph at Cesena.
The Italian forward will be out for at least two months.
"We are really sorry for Emanuele," Siena goalkeeper Gianluca Pegolo said. "Unfortunately, these things can happen and we just hope he will recover as soon as possible.
"He is a crucial player for us and we hope his absence will not hinder us too much."
Last weekend's success was Siena's third straight triumph and lifted Giuseppe Sannino's side to 14th place, seven points above the drop zone.
Pegolo is hoping his side can keep up their good run of form but knows Novara will be no pushovers.
"We passed an important exam at Cesena," he said. "We took home three important points.
"But we cannot let our guard down.
"We have to show the same determination game after game and keep climbing up in the standings.
"Novara are showing signs of recovery.
"They seem to have rediscovered their enthusiasm with the return of (coach) Attilio Tesser and their victory with Udinese.
"They will come here determined to take three points and we must be ready for a battle."
Tesser made a winning return to the Novara bench as his side defeated Udinese 1-0 last time out, thanks to Jeda's goal.
The win was Novara's first in three months and their fourth triumph of the campaign.
Tesser is hoping the win can act as a catalyst as his side look to beat the drop this season.
The Piedmontese side are in 19th place, 11 points behind safety with 11 games remaining.
"We need to give continuity to our win over Udinese," Tesser said. "We have to give our maximum in every game knowing that we face a huge task to defend our Serie A status."