Boston (46-22) won the first two games of the series, including Tuesday's 6-4 victory. Chris Sale (5-4, 2.83 ERA) will pitch for Boston on Wednesday against Yefry Ramirez, who will make his major-league debut.
Sale has lost his last three starts. He pitched well against the White Sox on Friday in his last start, allowing one run on six hits in eight innings -- with 10 strikeouts -- but still took the loss as Chicago scored a 1-0 victory.
He has pitched effectively against the Orioles in his career, going 5-2 with a 2.79 ERA in 15 games, including nine starts, and will try to give the Red Sox their ninth win in 10 games versus Baltimore this season.
The Orioles are struggling on offense right now, a big reason the team has lost six in a row and 13 of their last 15 games.
Ramirez will be called up from Triple-A Norfolk as the Orioles placed Andrew Cashner on the disabled list Tuesday due to a lower back strain. They also brought up relief pitcher Donnie Hart from Norfolk.
Cashner had been scheduled to start Wednesday's game but Ramirez instead will get his first chance to pitch in the majors.
The Red Sox also will have Mookie Betts in the lineup. Betts had been out since May 26 with a left abdominal strain before being surprisingly activated before Monday's 2-0 victory.
He went 1-for-5 and Red Sox manager Alex Cora took him out after the top of the 11th inning so Betts would not be pushed too much on his first day back.
Betts did not play in Tuesday's win, but he and Cora said it was more just to ease him back in slowly.
"He was going to play two out of three anyway," Cora said before Tuesday's game. "Yesterday we extended him a little bit. He'll start tomorrow."
Betts also leads the major league All-Star Game voting as the Red Sox likely will have a few players on the American League team.
The Orioles' best chance for that game will be Manny Machado, who returned to the Baltimore lineup Tuesday after missing a game due to an illness.
Baltimore ran into the same problems Tuesday that have plagued its lineup all season - an inability to score without homers and not being able to get the big hit at the right time.
The Orioles went just 2-for-13 with runners in scoring position and stranded 13 baserunners overall. There were just too many missed chances once again.
Baltimore has just a .227 team batting average after the Tuesday loss -- and it won't get any easier in the series finale with Sale starting and the solid bullpen waiting behind him.
"You've got a guy like Sale starting tomorrow," Orioles manager Buck Showalter told the media afterward. "They feel pretty confident about their bullpen. They've got eight of them down there."