Alfredsson, 40, has a minus-2 rating with one shot on goal in one preseason game.
Forward Johan Franzen also will not play. The team's website said he skated Thursday morning with the first group at Joe Louis Arena but is experiencing a painful hip flexor. Mikael Samuelsson will replace Franzen in the lineup.
Center Darren Helm (groin, lower back), who has not played in the first three exhibition games, skated for a short period Thursday morning. It was his first time on the ice since he injured the groin on Sept. 6.
Franzen said he hopes to be ready for the preseason home opener Saturday against the Bruins.
"I've had some similar stuff in the past, but I think it's usually kept me out like one or two games," Franzen told the website. "It's preseason now. It wouldn't be an issue if it where a playoff game. If that were the case we wouldn't even be talking about it. … I really don't want to risk anything."