He was placed on the 15-day disabled list Saturday after he broke a bone in his right hand. Middlebrooks was hit by a pitch in the ninth inning of Friday's game by Cleveland Indians reliever Esmil Rogers.
"He had a terrific run for us," Red Sox manager Bobby Valentine said. "He's a terrific player. I don't think he'll be back this year. He might for a short stint, I don't know.
"I couldn't be happier or more proud of everything he did and developing into the player that he did. It's a damn shame."
On the season, Middlebrooks batted .288 with 15 home runs and 54 RBIs.
"I see no silver lining of him not being in the lineup," Valentine said.
Third baseman Danny Valencia was acquired from the Twins on Aug. 5 in exchange for minor league outfielder Jeremias Pineda. Valencia was sent to Triple-A Pawtucket. He was recalled Saturday, but didn't arrive in Cleveland in time for the start Saturday's game.
Valentine commended Red Sox general manager Ben Cherington for the Valencia trade.
"Good job by Ben and his crew, trying to increase the depth at different positions," he said.
Valencia could get the bulk of the playing time at third. Pedro Ciriaco was at third against the Indians on Saturday.
"I have no idea (what we'll do)," Valentine said. "We'll figure it out, though. There are no concrete plans."
Mike Aviles, in the lineup at shortstop on Saturday, won't be shifted to third.
Valencia batted just .198 in 34 games with the Twins this season. Valentine said Valencia fell out of good graces with the Twins.
"There was something they didn't like over there," Valentine said.
The new scenery could be exactly what Valencia needs.
"We like his approach at the plate," Valentine said. "We like his defensive abilities. It seems like his head was in the right place."
Valentine said it's time players wear a protective apparatus on the wrist to prevent injuries like Middlebrooks'. He said two or three times every year players are sidelined with broken hands.
Meanwhile, Red Sox DH David Ortiz is experiencing some soreness in his strained Achilles. Trainer Rick Jameyson told Valentine that Ortiz's leg bothers him only when he runs straight ahead.
"He had off day yesterday and felt great," Valentine said. "Today he is going to hit and run.
"We are trying to make sure he has no setback."