Wolfe was in a pile during a running play in a team drill early in practice -- tackle Menelik Watson limped, flexing his own right leg following the play -- and stayed down. Trainers helped Wolfe onto a cart, and he was taken to the locker room.
Wolfe could not put any weight on the leg as he was helped inside the Broncos' complex.
"It's an ankle injury, we're not sure how bad," Broncos coach Vance Joseph said immediately following practice.
Asked about the severity of the injury, Joseph then added: "We're not sure about that, but the first look it wasn't serious, but we'll know more [Sunday]."
Wolfe was being sent for an MRI following practice, and the Broncos hope to have a potential timetable for a return to practice if the exam doesn't reveal more than the medical staff saw in the preliminary look.
Wolfe suffered a stinger early in training camp and was removed from drills for the remainder of that practice, but he returned to practice quickly in the days that followed.
Like the rest of the Broncos' starting defense, Wolfe didn't get much work in Thursday night's preseason opener in Chicago. Wolfe played just three plays in the Broncos' 24-17 victory at Soldier Field.
The starting defense played the opening three plays but were taken out of the game after cornerback Chris Harris Jr. returned an interception 50 yards for a touchdown on the third play of the game.
The Broncos have wrestled with some high-profile injuries so far in camp;running back Devontae Booker (left wrist) and linebacker Shane Ray (left wrist) will miss the entire preseason. Defensive end Billy Winn suffered a season-ending knee injury in the win over the Bears as he tore his right ACL.
The Broncos signed defensive lineman Nelson Adams, who had recently been waived by the Pittsburgh Steelers, when Winn was formally moved to injured reserve.