Cabrera, who leads the majors with 126 RBI and is among the AL's leaders in several other offensive categories, has a sprained right ankle.
Manager Jim Leyland announced before the start of a doubleheader against the Cleveland Indians that Cabrera will not play again in 2010.
"It seems strange not putting Cabrera's name in there," Leyland said before the Tigers were blanked 1-0 by the Indians in the opener. "It wasn't broken. That's a blessing. He's got a long time to heal up."
Cabrera was injured on a pickoff attempt at first base Monday night and hoped to return during Detroit's final six games. An MRI exam performed Tuesday night revealed a high ankle sprain and Cabrera will not accompany the team to Baltimore for its final four-game series.
Leyland said if the injury had occurred earlier in the season that Cabrera, who is wearing a walking boot, would have been placed on the disabled list and would miss at least three weeks.
Cabrera is tied for second in the AL with 38 homers and is hitting .328, third in the league. Leyland thinks he should win the voting for the league's MVP award.
"I think he's been the best player in the league this year," Leyland said. "I don't want to be on a soap box. I think he's the MVP and I'll leave it at that."
Cabrera's production has included a league-high 32 intentional walks.
"He probably gets more respect from an offensive standpoint than any hitter in the league," Leyland said. "There aren't many guys who can do what he can do. They've been trying to pitch around him and he's still hitting homers."