Baltimore can put an exclamation point on the three-game set, after pulling out a 6-4, 13-inning victory Friday and hammering the Red Sox, 8-2, on Saturday.
Baltimore has won 10 of its last 12 and continues to chase the Rays at the top of the division standings. Conversely, Boston, which is 0-2 so far on a seven-day, six-game homestand, has lost its last four games and nine of 10.
"You have to look at the little victories when you play well," Boston skipper Bobby Valentine said of working through his club's struggles. "What are you going to do -- discount the little things that went well and say, 'Oh well, we lost, so all the good things don't count?' I think a lot of good things happened, and guys have to not lose sight of that. Just keep doing the good things."
To stop the bleeding, the Red Sox will turn to right-hander Clay Buchholz, who allowed just one run until there were two outs in the seventh his last time out. He then surrendered five more and has not had a start in which he's allowed fewer than five runs.
Baltimore will counter with righty Tommy Hunter, who will be working on two extra days of rest since dealing with an ingrown toenail that was removed. He hopes to be fresh for Sunday's series finale.
"I just want to give him a couple extra days and get him back to 100 percent," Orioles manager Buck Showalter said earlier this week. "He'll tell you that he is, but we had an opportunity and we'll see if we can give him a couple extra days there."
Hunter last pitched seven innings of two-run ball against the A's on April 29.
Orioles: Pen is mighty
Baltimore relievers have combined to throw 21 consecutive scoreless innings since April 27.
Since Sept. 12, 2011, the Orioles have gone 11-2-1 in 14 series and are 29-15 in their last 44 games.
Baltimore, which is 2-0 against the Red Sox this year, has not won a season series against Boston since going 10-9 in 2004.
Red Sox: Gonzalez coming around
Adrian Gonzalez has struggled this season, but he went 3-for-6 on Friday and picked up his first extra-base hit since April 26 in a 3-for-4 effort on Saturday.
Valentine said he thinks Gonzalez is ready to break out.
"I don't know his swing that well, so I'm not going to speak on his swing," he said. "But he says he's feeling better, and that's what's important."
Third baseman Will Middlebrooks, who had two hits in his debut on Wednesday against the A's, was scratched late Saturday with tightness in his left hamstring. He is considered day to day.
After their afternoon loss on Saturday, the Red Sox dropped to 7 1/2 games back of the first-place Rays, who played later that night. It's Boston's largest deficit in the standings this year.
The Red Sox are in a stretch of 20 games in 20 days between off-days from May 4-24. Nine of the games will be at Fenway Park, and 11 are on the road. They're 0-2 to begin the stretch.