Matt Cullen and Peter Regin each added a goal while Erik Karlsson racked up three assists as the Senators claimed their fourth straight win, strengthening their hold on the fifth spot in the Eastern Conference standings, five ahead of Montreal and six points in back of New Jersey.
Brian Elliott stopped 20 shots in Ottawa's win.
Ottawa got a crucial two-goal cushion at 1:44 into the third period during a power play when Alfredsson's slap shot from the left point flew past Panthers goalie Tomas Vokoun to make it 3-1.
After Cory Stillman scored on a 5-on-3 situation to make it 3-2, Florida had another two-man advantage late in the game but couldn't dent Elliott. Stephen Weiss and Steven Reinprecht got the Panthers' other goals.