Manager John Farrell said the move was precautionary and was hopeful Ortiz would return Friday.
"[We] just have to manage the condition and the situation he's dealing with," Farrell said before Thursday's 4-3 win over the Atlanta Braves.
Ortiz was able to enter Thursday's game as a pinch hitter in the eighth inning. He was intentionally walked and promptly removed for a pinch runner, Mike Carp, who's battling a lingering foot ailment that kept him out of Wednesday's game. Carp received X-rays on his foot Wednesday that came back negative.
Ortiz has dealt with calf issues at several points this season, including during last weekend's series against the Rays that required him to miss a start on Saturday.
"After two full days at first base [in Atlanta] and another at DH last night, it was best to hold him out tonight," Farrell said. "This is precautionary, just want to not put him at risk any further."
A.J. Pierzynski took Ortiz's spot in the lineup, playing DH and batting fourth.
David Ross was behind the plate for the Red Sox, and the club's third catcher, Ryan Lavarnway, made his first career start at first base. But Lavarnway was lifted for pinch hitter Daniel Nava in the fifth inning because of a sore left wrist Lavarnway aggravated in his first at-bat. Farrell said Lavarnway would have an MRI on Friday.
Ortiz leads the Red Sox in a number of offensive categories, including homers (12), RBIs (30), total bases (94) and OPS (.880).
Meanwhile, starter Clay Buchholz, placed on the disabled list Wednesday with a hyperextended left knee, will not participate in throwing or baseball activities until Saturday at the earliest. In the meantime, Farrell said that Buchholz will undergo treatment to determine whether or not he is ready to return to pitching from a mound on Saturday.
As for Buchholz's spot in the rotation, Farrell mentioned several candidates who could take the mound on Saturday against the Tampa Bay Rays, including Allen Webster (2-2, 3.17 ERA at Triple-A Pawtucket), Rubby De La Rosa (2-3, 3.04 ERA) and prospect Anthony Ranaudo (5-3, 2.90 ERA).
Farrell maintained that there is still no temptation to move reliever Chris Capuano from the bullpen to the rotation, where he primarily pitched during the first nine years of his career.
In other injury news:
• Starter Felix Doubront will throw long toss on flat ground Thursday out to 120 feet. Doubront was placed on the disabled list May 21 with a left shoulder strain.
• First baseman Mike Napoli's dislocated left ring finger is improving, according to Farrell. With the swelling in his finger starting to diminish, Napoli went through several baseball activities on Thursday, including baserunning drills. Farrell said the team is hopeful to get a bat back in his hands shortly and that the calf and hamstring issues he dealt with earlier this season are no longer a problem.
"With everything that was involved, the fact that he's now four days past the decision of putting him on the DL, he's been able to get ahead of [those issues] somewhat," Farrell said. "The running is to keep him in game shape, or as close to it, as we can."
Napoli was placed on the disabled list Sunday. Lavarnway made 26 starts at first with Triple-A Pawtucket earlier this season after moving from catcher during spring training.
"We saw in spring training we wouldn't have any hesitancy to play him there," Farrell said. "Against a left-handed starter [Atlanta's Mike Minor], he fits."
Farrell added, "To his credit, he's worked hard at being accomplished, or at least capable, at the position."
• No date has been set for outfielder Shane Victorino's return as he is still responding to treatment for his strained right hamstring, which landed him on the DL on Saturday. Farrell said that because this is the second time Victorino has spent time on the disabled list with a hamstring injury this season, the team will be cautious with his recovery. "He's going to be out there when he's capable," Farrell said. "I don't have a date or a number of days that we're looking at on the calendar yet."
• Farrell had no updates to provide on third baseman Will Middlebrooks (finger), although he mentioned that his range of motion has improved. Middlebrooks was placed on the disabled list May 17.
Kyle Brasseur contributes to ESPNBoston.com's Red Sox coverage.