The crash happened about 1 p.m. Wednesday on M-32 near Johannesburg in Otsego County, said Sgt. Tony Harrington at the state police post in Gaylord. He said details on the crash and the victims' identities weren't yet known.
Earlier weather-related crashes have claimed at least four lives in the state, and a man in Paw Paw died of a heart attack while clearing snow.
Dangerously cold wind chill temperatures eased somewhat in Michigan, but officials kept many schools closed for another day Wednesday.
The temperature dipped to minus 6 early Wednesday in Three Rivers in the southwestern Lower Peninsula, according to the National Weather. Statewide temperatures were mainly in the teens Wednesday afternoon.
Winds were making it seem much colder, however, and increasing the risk of injury.
"Frostbite of exposed skin can occur in a matter of minutes in these conditions," the weather service said in advisory.
The school closing lists shrank Wednesday, with schools including the University of Michigan in Ann Arbor, Eastern Michigan University in Ypsilanti, Wayne State University in Detroit and Central Michigan University in Mount Pleasant holding classes.
Still, hundreds of Michigan elementary, middle and high schools were shut Wednesday. All Detroit public schools closed for another day. Students in Flint Community Schools had their third consecutive day off because of cold weather. Many schools in western Michigan remained closed Wednesday.
"The bottom line is safety," Rockford Public Schools Superintendent Mike Shibler said. "The roads are better but still pretty bad, particularly secondary and country roads. The wind chill is still really low so the salt is not working and it is unsafe for kids to travel to school either by bus or with their parents."
Crews in Lenawee County encountered 10-foot-high snowdrifts while working to clear roads in rural areas. County Road Commission operations manager Jason Schnaidt said the roads were "passable" but that more work remained.
"We've made a hole in them. Nothing that looks very pretty, but we've made a hole so people can get in and out," he said.
Drifting snow has been a problem in Lenawee County since Saturday. The winds eased Tuesday, making it less of an issue.
In Grand Rapids, a pavilion that for years served as a gathering place for church groups, fundraisers and family reunions collapsed Monday under the weight of snow. No injuries were reported. The pavilion seated 400 people, and the Christian Reformed Recreation Center plans to rebuild.