Ellsbury, who has been on the disabled list since the end of May with fractured ribs, is expected to be activated for Wednesday's game, bat leadoff and play center field.
Boston will hand the ball to left-hander Jon Lester this evening, as he tries to stop a personal three-start losing streak. Lester absorbed the loss on Friday against Detroit, yielding four runs and 11 hits in six innings to fall to 11-6 on the year to go along with a 3.05 earned run average.
"It was just one of those nights. You're going to have ones where you don't feel good," Lester said. "There was no rhythm, no balance, no execution."
Lester has faced the Indians three times and is 3-0 against them with a 4.65 ERA in seven starts.
Cleveland, meanwhile, will counter with righty Justin Masterson, who is a dismal 3-10 on the season with a 5.55 ERA. Masterson, a second round pick of the Red Sox in 2006, was roughed up by the Toronto Blue Jays on Friday for eight runs and 13 hits in just 5 1/3 innings.
Masterson, the centerpiece of last year's deal that landed Victor Martinez in Boston, tossed a two-hit shutout to beat his former team back on June 9 in his only other start against them.
After dropping the opener of this set, the Red Sox pulled even on Tuesday, as Mike Lowell hit a two-run homer in his return from the disabled list and Josh Beckett turned in eight strong innings, helping Boston to a 3-1 triumph.
Beckett (3-1) gave up just one run on three hits, fanning eight without a walk for his second straight win.
"Beckett was very good -- he threw his breaking ball very well tonight," said Boston manager Terry Francona.
The 30-year-old, who missed more than two months from mid-May to late July, posted his first home victory of 2010 with the effort but was ejected late in the game for his role in a mutual bench-clearing event.
"I am feeling good," said Beckett. "The coaching staff is allowing me to steadily build up my stamina."
Bill Hall also homered for the Red Sox, who won their sixth game in eight tries thanks in part to Jonathan Papelbon's 25th save with a scoreless ninth.
Lou Marson's solo homer was the lone offense for the Indians, whose three-game win streak was halted.
David Huff (2-10) was tagged in the loss for seven hits and three runs over 5 1/3 frames.
Cleveland has split its six games with the Red Sox this season after losing seven of nine to them a season ago.