Youkilis was a late scratch due to a sore left hand, reportedly from a dive he made in the field Tuesday night. Drew is sitting against a right-hander because of a sore right hamstring, which he received making a running catch in the ninth inning Tuesday.
Drew Sutton, who started in Pedroia's place last night, will play third base with Youkilis out. Mike Cameron is playing right field in place of Drew.
Pedroia, mired in a month-long slump, was showing slight signs of a turnaround before his fall the other night. He is 5-for-16 (.313) with three walks and two stolen bases in his last four games overall.
Additionally, Pedroia is one of a handful in Wednesday's batting order to have had some success against Cleveland Indians starter Mitch Talbot. He is 3-for-7 (.429) with a pair of RBIs against the young right-hander.
As a whole, Boston's lineup is 9-for-26 (.346) with a home run, two doubles and four walks against Talbot.
Carl Crawford, who homered and scored twice in the series opener, was originally penciled into the seventh spot in the lineup but was bumped to sixth with the insertion of Sutton into the nine-hole. It marks the first time in his career that Crawford has started a game batting sixth.
Cameron settles in behind Crawford in the eighth spot. Cameron has been giving Drew days off against left-handers but is getting a rare start against a righty due to Drew's hamstring issue.
This is the first time all year that Cameron has batted eighth.
Here is a look at the complete batting order in support of Jon Lester, followed by Cleveland's lineup.
Red Sox
Jacoby Ellsbury, CF
Dustin Pedroia, 2B
Adrian Gonzalez, 1B
David Ortiz, DH
Jed Lowrie, SS
Carl Crawford, LF
Jarrod Saltalamacchia, C
Mike Cameron, RF
Drew Sutton, 3B
Indians
Michael Brantley, CF
Asdrubal Cabrera, SS
Shin-Soo Choo, RF
Shelley Duncan, DH
Matt LaPorta, 1B
Austin Kearns, LF
Jack Hannahan, 3B
Lou Marson, C
Adam Everett, 2B
