Wolfe appeared unable to put any pressure on his right leg as he was helped by trainers from the cart into the team's facility.
That's very bad news for Wolfe, and for the Broncos defense. His backup Shaq Barrett will miss more time because of a hip injury. Strong safety T.J. Ward has been out with a hamstring injury. The Broncos made one move to bulk up the line on Saturday, but another potential loss could set them back even further than they started the day.
Winn was caught under the pile on a Bears run in the first quarter of the Broncos' exhibition game in Chicago.
In each of the past two seasons, Wolfe has notched 5.5 sacks.
Derek Wolfe ankle injury not considered serious
That performance earned him a four-year extension worth $36.7 million just before the Broncos' victory in Super Bowl 50 over the Carolina Panthers.
Should Wolfe miss the rest of the preseason, the 3-4 defensive ends next in line for the Broncos are Adam Gotsis, Zach Kerr and Shakir Soto.
The Broncos, who edged the Bears 24-17 to start the exhibition slate, will be back in action on August 19 when they travel to San Francisco.