Both players suffered the injuries during training this week and will also miss the Champions League clash with Celtic on Tuesday.
A statement from Milan read: “AC Milan announces Cristian Zaccardo has suffered a sprain in his left ankle.
“The defender’s condition will be evaluated in the next coming days to determine a prognosis.
“Marco Amelia will undergo surgery in his left knee today (Friday) having sustained a meniscus injury.”
The Rossoneri are currently 10th in the Serie A.