The goal, assisted by Zetterberg and Justin Abdelkader, came after Detroit's power play had expired and gave them a 2-0 lead over the Oilers.
But later in the first, Nyquist appeared to go knee-to-knee with Edmonton defenseman Eric Gryba and he had to leave the game.
The Wings announced later that Nyquist had suffered a lower-body injury and would not return.
"I would say right now it's day to day," Wings coach Jeff Blashill said after the game. "I did not check with (athletic trainer) Piet Van Zant to see the availability of tomorrow yet. I just found out he wasn't coming back. I think it's a long-term thing but he might not be available tomorrow."
Currently, the Wings do have David Booth and Luke Witkowski, both healthy scratches, available for Monday's game in Vancouver.
"It's tough," Frans Nielsen said. "He's one of our more talented players and better players, so hopefully it's not too serious. It's always tough to lose anyone but especially a guy like that."
Nyquist is tied for second on the team in goals with Nielsen, who scored the first goal in Edmonton.
Mantha leads the team with seven goals.
