Pedroia suffered the injuries when he was spiked by the Orioles' Manny Machado on Friday. He didn't play Saturday or Sunday.
Red Sox manager John Farrell said Pedroia would have played Tuesday if that game had not been rained out. However, Farrell said Pedroia woke up Wednesday with "lingering symptoms" of soreness, and the wet conditions also played a factor in keeping him out of the lineup.
"When Dr. [Peter] Asnis examined him [Monday], he felt like there was still strong stability in the knee," Farrell said. "Recognizing there was still some swelling in the ankle and somewhat around the knee area, given the impact that took place, we didn't think this was going to be completely gone in a matter of two or three days."
In other roster news, relief pitcher Matt Barnes will start serving his four-game suspension on Wednesday after dropping his appeal. He also was fined an undisclosed amount for throwing a fastball past Machado's head during Sunday's game.
Barnes, who wasn't available for comment Wednesday, is eligible to return Sunday night against the Cubs. In his absence, the Red Sox likely will use Heath Hembree as their primary eighth-inning reliever.
ESPN Staff Writer Scott Lauber contributed to this report.