Giddey had laid off a pass unchallenged before clutching at his left hamstring and then limping off the court into the locker rooms for further assessment.
The state of his condition was not immediately known to the public, but if the 23-year-old has suffered a Grade 2 (partial tear) injury, his maiden All-Star selection could be in jeopardy with the recovery time for such injuries usually ranging between four and eight weeks.
His exit came on a horror night for the Bulls, who also lost Coby White to a calf injury after just seven minutes, and are now without their two leading scorers - Giddey averaging 19.5 points per game and White 20.5ppg - for the foreseeable future.
Giddey's untimely injury came just hours after the first round of fan voting for mid-February's All-Star weekend was revealed. The Australian had received more than 115,000 votes and was the 14th-most popular pick for the Eastern Conference, which under the traditional format could earn him the final reserves position.
The newly reformatted All-Star weekend will see three sides - two composites with American players and a 'World team' - play in a round-robin tournament with a final, though traditional non-playing East and West All-Star teams will still be named.
The Australian is a significant chance to be a starting guard alongside Luka Dončić in the World team if fit.