Chandler collided with Brooklyn forward Gerald Wallace and appeared to be in significant pain. He stayed on the ground clutching his knee and was tended to by a Knicks trainer before heading back to the locker room.
The Knicks announced shortly thereafter that Chandler would not return due to the knee ailment. The team says it's a minor injury and Chandler was held of the game out as a precaution.
Guard/forward James White also left the game in the third quarter with a sore left foot.
The Knicks are playing their last preseason game and have eight days before their season-opener on the road against Brooklyn on Nov. 1.
New York has suffered through several injuries during the preseason.
Marcus Camby has missed the entire preseason with a calf injury. J.R. Smith has sat out the final four preseason games with an Achillies injury. Amare Stoudemire is expected to miss two more weeks due to a ruptured cyst in his right knee and Rasheed Wallace is unavailable due to conditioning issues.
The Knicks have the oldest roster in the NBA, with an average age of 31, so health is a concern coming into the season.