Minnesota has now lost seven of nine to the Tigers this season.
Pelfrey (3-1) was tagged with his first loss of the season. He gave up five runs (four earned) on 10 hits, while he struck out one and walked two, in 4 2/3 innings.
Miguel Cabrera homered twice for Detroit. He finished the afternoon 3-for-5 with a pair of homers, 5 RBIs and three runs scored.
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Nick Costellanos and Bryan Holaday also homered for the Tigers. Anthony Gose was 4-for-5 with a pair of runs scored. Seven Tigers players had multiple hits as the team pounded out 20 hits in the game.
It was more than enough run support for Tigers' starter Anibal Sanchez (3-4). He went eight innings, gave up just one run on five hits and struck out nine to pick up the win.
Eduardo Escobar drove in the only Twins run, he finished 1-for-3 on the afternoon.
The Twins return to Target Field on Friday night to play Tampa Bay. Phil Hughes (2-4) takes the mound against Jake Odorizzi.