Miami fell to 4-13 in June after a 15-5 drubbing in the second game of a three-game set with the Red Sox. The 15 runs were the most Miami has allowed this season and Boston's 16 hits off Marlins pitchers matched the most surrendered by the team in 2012.
The loss dropped Miami two games under .500, while the Red Sox moved two games over .500 and out of last place in the American League East.
Thursday's pitching matchup will feature Boston's Daisuke Matsuzaka against Miami's Carlos Zambrano.
Matsuzaka has lost his only two starts this season since coming back from Tommy John surgery and will once again be looking for his 50th career win, which would make him the third Japanese pitcher to accomplish the feat. He threw six innings and 93 pitches his last outing, both of which were season highs.
"Dice-K's got to come out and give us a clean first inning, give us a chance to have the bats get alive without trying to climb back into one," Red Sox manager Bobby Valentine said.
Matsuzaka allowed two runs in the first inning of his last start.
Zambrano, meanwhile, has struggled after a strong start to his Marlins career. The veteran right-hander has lasted just 4 1/3 innings his past two starts combined and surrendered 11 runs while walking nine during that span to fall to 4-5 on the year.
"I think Carlos right now is a little out of whack," Marlins manager Ozzie Guillen said. "His mechanics are very bad, his sinker is moving way too low. When you throw ball one, ball two, you are going to be in the middle of the plate and you are going to be hit. You cannot get behind people walking them all the time. Pitching is not about how hard you throw, it's about location and what you want to do on the mound. I think Carlos will be fine."
Boston is looking for its fifth consecutive win, which would be one short of its season high, set in the first month of the season.
Red Sox: First-round pick Marrero signs
The Red Sox agreed to terms with shortstop Deven Marrero, the club's first pick of the 2012 First-Year Player Draft.
While no numbers were finalized, it was expected Marrero would be signing for $2.05 million, which would be above the recommended $1,750,000 value for the No. 24 overall pick.
Marrero was at Fenway Park on Wednesday mingling with the team, took batting practice and will report to the Class A Lowell Spinners on Thursday.
Like Red Sox second baseman Dustin Pedroia, the 21-year-old went to Arizona State and had a chance to chat with him on Wednesday.
"They both went to the same college, their style of thinking, their aggressiveness, team play, winning -- they're all of the same ilk," said Marrero's agent, Scott Boras, who was also in attendance Wednesday. "It's very nice for Deven that he gets to play with someone I think he admires and has a lot of the qualities that Deven aspires to have."
Boston is also expected to sign its other first-round pick, University of Florida left-handed pitcher Brian Johnson, by the weekend.
Pedroia, who has a torn adductor muscle in his right thumb, sat out Wednesday's contest against the Marlins after getting jammed in the seventh inning of Tuesday's game.
The move was precautionary and the former AL MVP plans to play Thursday.
"My hand slipped off the bat and my thumb got caught," Pedroia said. "It was just kind of a weird feeling. I'm not playing today [Wednesday], but I'll be in there tomorrow [Thursday]. I feel fine."
David Ortiz hit his 10th grand slam as a member of the Red Sox in the fourth inning of Wednesday's win off Marlins reliever Chris Hatcher, and moved into second place on the Red Sox all-time grand slam leaderboard. Ted Williams holds the record with 17.
The homer was the 396th of Ortiz's career, 18th of the season and third in as many days. Ortiz is enjoying another fine season, batting .313 with 49 RBIs and a 1.011 OPS.
Marlins: Infante slumping
Omar Infante has struggled mightily after starting off the season hot.
The Marlins second baseman was batting .340 on May 25 but entered Wednesday's contest with that mark down to .280 on the year, and .180 for the month of June.
Over the first four games of the Marlins' six-game road trip he went 1-for-15, before busting out of the slump with a 3-for-4 effort in Wednesday's loss.
Guillen did not shy away from Infante's problems at the dish.
"He was the best hitter I had all year long and all of a sudden he's not," Guillen said.
Catcher John Buck homered over the Green Monster to lead off the seventh inning but cramped up and came out during his ninth-inning at-bat. He's expected to be in the lineup on Thursday.
Buck is 5-for-10 lifetime against Matsuzaka and one of only four Marlins players who have ever faced him.
Zambrano has held this current version of the Red Sox to a .216 average and .635 OPS over 88 at-bats. Ortiz is the only Red Sox player to hit a homer off him.