The Wolverines (2-4) will end the 2020 season winless at home.
Saturday's Michigan-Iowa game has been canceled due to COVID-19 issues, the Wolverines announced on Tuesday.
The two schools were slated to face off as part of the Big Ten's Champions Week.
Michigan athletic director Warde Manuel said the program had more than 50 players unavailable to play compared to the previous week.
With Saturday's game being canceled, Michigan's season is over.
The Wolverines (2-4) will end the 2020 season winless at home and with only two wins for the season. It also marks the program's first losing season since going 5-7 in 2014 under coach Brady Hoke.
In three home games this year, the Wolverines lost to Michigan State, Wisconsin and Penn State. Michigan last had a losing record at home in 2008, when the team went 2-4 at the Big House in Rich Rodriguez's first season.
Prior to the Iowa cancellation, Michigan's previous two games against Maryland and Ohio State were canceled due to COVID-19 issues. The program said last week that it would not have enough healthy players to participate in "The Game."
After Michigan canceled the rivalry game against Ohio State, the Wolverines returned to the weight room on Thursday and Friday before practicing on Sunday and Monday.
Jim Harbaugh, who just finished his sixth season as Michigan's head coach, is slated to begin discussions over a possible new contract. His initial deal expires after the 2021 season, but Harbaugh and Manuel have said they would discuss the contract following the 2020 season.
Iowa (6-2) has won six consecutive games after starting the season 0-2. If the Hawkeyes cannot find another opponent to play this week, they will wait for their bowl game selection.
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