Zetterberg will miss at least the next two weeks, starting Wednesday night against the visiting Philadelphia Flyers as Detroit looks to extend its winning streak to five games.
Datsyuk, who has a team-best 12 goals, has been sidelined for the last four contests due to a head injury and is doubtful to play Wednesday, though he could return soon.
Detroit (14-7-7) has made do without him, outscoring opponents 18-4 during its streak. Drew Miller scored twice and Daniel Alfredsson had a goal and an assist in a 4-2 win over Ottawa on Sunday.
Zetterberg didn't record a point, and he'll now miss time with a small herniated disc, according to general manager Ken Holland. The forward, who leads the team with 30 points (11 goals, 18 assists) and is tied for first on the Wings at plus-12, could be out even longer.
"He was a force at the end of last year and he's probably been our best player this year," goaltender Jimmy Howard told the team's official website. "Night in and night out, he's finding ways to put pucks in the net for us or setting guys up."
Detroit will need to continue getting scoring from elsewhere with Zetterberg and Datsyuk out. Alfredsson has four goals and three assists during the Red Wings' run, while defenseman Niklas Kronwall has two goals and seven assists during a six-game point streak.
"For a while there no one scored except Pav and Hank, so obviously (Alfredsson has been) huge for us," coach Mike Babcock said. "We need him going. Leadership's key on any team. I think Alfredsson coming has given us another guy.
"When things go good it's not as big a deal. When things go bad, that's when you need to be stable, and I think we've been good that way."
Alfredsson recorded three assists, Zetterberg had two goals and an assist and Datsyuk and Kronwall added a goal and two assists apiece in a 5-2 win over Philadelphia on Oct. 12. Howard made 32 saves.
Jonas Gustavsson is 7-0-1 with a 1.99 goals-against average in his eight starts this season after making 30 saves against the Senators. It's uncertain if he or Howard will be in net against the Flyers (12-13-2).
Philadelphia went 8-2-1 in its previous 11 before falling 2-0 to Minnesota on Monday in its second stop on a six-game road trip. It scored fewer than three non-shootout goals for the fifth straight time and its 57 goals are among the fewest in the league.
Vincent Lecavalier, who has a team-best nine goals, was scratched in the last contest because of back spasms. His status for this game is uncertain.
"It's unbelievable this year, so many chances," said Voracek, who scored a career-high 22 goals in 46 games last season. "I hit a couple posts, a couple good saves. Last year everything went under the bar. ... This year I think it's going to go in and then something happens."
Ray Emery made 19 saves Monday, but Steve Mason -- 6-1-1 with a 1.72 GAA in his last eight -- could start this contest.