The injury happened on a play in which Guillen wasn't involved, a ground ball to the right side that pitcher Justin Verlander fielded before throwing to first for the out on Jemile Weeks. But as Weeks was heading back to the dugout, Guillen was limping. He was helped off the field by the Tigers medical staff. Ryan Raburn replaced him at second base.
Guillen said he broke for first base on the ground ball in case he needed to cover the bag, and the calf "grabbed" at him.
Manager Jim Leyland didn't sound optimistic when asked about the chances of Guillen returning to action soon.
"I don't really know the answer to that yet," Leyland said. "I don't think it's going to be a short-term thing. He was limping pretty good. ... Calf muscles are usually not a good one, to be honest with you, but I don't really know the severity of it."
The malady is the latest in what has been an injury-plagued season for Guillen, who missed the first half of the season recovering from microfracture surgery on his left knee before going back on the disabled list in early August with right wrist soreness. He missed about three weeks before returning Sept. 1 once rosters expanded.
Guillen has played sparingly since. Sunday was just his second start in two weeks. Raburn and Ramon Santiago have split much of the second-base duties since Guillen went on the DL in early August.