Police say they approached the man near the Dyer Road overpass and the 55 Freeway early Sunday morning, fearing he was about to jump.
They say that's when the man, who was only dressed in a T-shirt and shorts, bolted back and forth across the freeway lanes.
They say he eventually decided to lie down in the southbound HOV lane.
"Officers at that time were able to take custody of him. There was a physical struggle when they took him into custody. When that occurred, the subject stopped breathing. Officers un-handcuffed him and performed CPR for a total of eight minutes," said Cpl. Anthony Bertagna with the Santa Ana Police Department.
The man was taken to the hospital in critical condition. In addition to the police investigation, the District Attorney's Office and internal affairs are also looking into the incident.
Officers say there was no shooting, nor was a Taser ever used.