Both players were hurt in Thursday's 8-2 win at Toronto.
Alfredsson, the team captain, has "upper body and knee" injuries, while Fisher was involved in a knee-to-knee collision.
Maple Leafs left wing Mark Bell was involved with both players.
Coach Bryan Murray said his players' down time was not known.
"I don't know the time frame but it's going to be awhile," Murray said on Ottawa's Web site. "We're talking weeks for both of them."
"It's obviously very frustrating but I'm hoping I can come back quick and help out," Alfredsson said.
He has 89 points this season (40 goals, 49 assists) and Fisher has 47 (23 goals, 24 assists).
The Senators locked up an Eastern Conference playoff spot Friday when Florida topped Carolina 4-3.
The Senators' opponent has not been determined.