Manager Joe Girardi estimated that Pettitte will be out until sometime in September after his latest setback, which occurred while he was throwing a bullpen session off a mound before the game.
Pettitte said through a spokesman that he felt discomfort when he tried to throw a pitch all-out, so he requested an MRI. The Yankees said the test showed "a small persistent strain."
Pettitte will not throw off a mound for another week, the Yankees said.
"It obviously hurts," general manager Brian Cashman said. "You can't replace an Andy Pettitte. But I've got to say, Dustin Moseley has done a good job."
Pettitte has been out since July 18. The team originally estimated he would miss as much as four-to-five weeks, a timeline Pettitte initially scoffed at. But now that timeline looks to be on the low end.
"We're expecting him probably sometime in September to be active," Girardi said.
Rodriguez also was sent for an MRI before last night's game and that test revealed "a low-grade strain" of the left calf, the Yankees said.
Girardi said Jorge Posada missed six games with a similar injury earlier this season and he doesn't expect Rodriguez to miss that much. But it's not going to be a one-day injury, either.
"I would think it would be at least a few days, including [Tuesday]," Girardi said. "We'll just play a little short until we get him back."
Rodriguez said he initially felt discomfort in his left calf before Monday night's game and trainer Steve Donohue treated him with heat. But he said the discomfort returned as he was running to first base when he flew out to rightfield during his second at-bat of Monday night's game.
"I've been very fortunate to be a quick healer," he said. "Keep my fingers crossed."
Rodriguez said he felt "surprisingly better" Tuesday than he expected to, but the Yankees still believed the injury was serious enough to warrant an MRI.