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Blackburn allowed four hits, including a Jim Thome homer, in 6 1-3 innings of Minnesota's 1-0 loss at Chicago in Game 163 last Sept. 30. The result sent the White Sox to the postseason for the first time since winning the World Series in 2005.
"Right back at it," Blackburn told the Twins official Web site about returning to face the White Sox.
The right-hander (0-0, 7.20 ERA) will try for a better outing after allowing four runs and eight hits while walking three in five innings of the Twins' 6-5 win over Seattle on Tuesday.
He is 2-3 with a 4.86 ERA in six starts against the White Sox (2-3), who snapped a three-game losing streak with an 8-0 win over Minnesota (3-3) on Saturday.
Behind seven strong innings from Bartolo Colon, Chicago bounced back from a 12-5 loss in Friday's series opener.
Even though regulars like Thome, A.J. Pierzynski and Chris Getz had the day off, the White Sox posted their most runs of the season after scoring 10 in their first four contests combined.
"It's not easy to keep everybody sharp," Chicago manager Ozzie Guillen told the team's official Web site. "The way we swing the bats, I try to get the lineup (for a) different look. When you're not swinging the bat as a team, that can get contagious."
Carlos Quentin went 2-for-4 with a homer and Alexei Ramirez snapped an 0-for-14 start with two hits and two RBIs for the White Sox, who were batting .200 with 31 strikeouts entering Saturday's game.
Chicago had been hitting .154 with runners in scoring position through the first four games, but went 5-for-12 in those situations Saturday.
Quentin is 4-for-10 with two homers and three RBIs since opening the season 0-for-6. He is batting .409 (9-for-22) with three home runs and eight RBIs in his last five games against Minnesota, and is 3-for-9 with a homer off Blackburn.
Pierzynski and Thome, who should be back in the lineup for the series finale, are a combined 10-for-26 with five RBIs against him.
Mark Buehrle (0-0, 3.60) looks to bounce back from a mediocre opening-day start for Chicago.
The left-hander allowed two runs and six hits while walking three and hitting two batters in five innings of a 4-2 opening-day win over Kansas City.
"As bad as I pitched and to keep them to only two runs, I'm happy about it," said Buehrle, who is 21-13 with a 3.78 ERA in 35 starts against the Twins, but went 1-3 with a 5.26 ERA versus them in 2008.
Michael Cuddyer is batting .304 lifetime against Buehrle - one of seven current Twins hitting better than .300 against him. Cuddyer went 2-for-4 on Saturday for Minnesota, which had only six hits after pounding out 15 on Friday.