Los Angeles Fire Department paramedics responded to the incident in downtown Los Angeles about 9:30 a.m. Sunday, the Los Angeles Times reported.
The man, identified as Charles Whitmore Riske of Costa Mesa, collapsed about 2 hours into the race. Paramedics attempted life-saving measures before Riske was taken to the hospital and pronounced dead.
His cause of death had not yet been determined.
"We are deeply saddened by this tragic loss, and our heartfelt sympathies go out to the runner's family and loved ones," said Dr. Lewis Maharam, medical director of the Competitor's Group Rock 'n' Roll marathon races, which are held across the country.
Fire Department spokesman Erik Scott said it was the only serious health issue connected to the race, which had more than 8,000 participants.