Henrik Zetterberg delivered a goal and an assist for Detroit, which has lost four in a row and 10 out of 11.
The Red Wings seemed to have the best record in the NHL wrapped up a month ago, but they now have only a three-point lead over Dallas.
Pavelski wristed a shot past Dominik Hasek just 1:40 into the game and Setoguchi put a one-timer over Hasek's glove 52 seconds into the second period.
This was the seventh game on San Jose's eight-game road trip and the Sharks downed the Red Wings for the first time in four tries.
Notable deaths of 2014 [PHOTOS]