Authorities said a Ford Explorer and a Lexus RX 350 crashed about 3:30 a.m. near the Artesia Boulevard off-ramp.
"We heard the horrific collision from the impact and then everybody started scrambling," said Mike Gillespie, a worker at the scene. "Two guys got killed for no reason."
Both road workers, identified as 56-year-old Ramon Lopez of Chino Hills and 58-year-old Ricardo Zamora of Winchester, were struck and killed. A third worker suffered minor injuries.
The driver of the Ford was 23-year-old Yocio Jonathan Gomez, of Norwalk, and the driver of the Lexus was 43-year-old Stephen Christopher Caserta, of Playa Vista, authorities said. Both drivers were arrested at a hospital on suspicion of driving under the influence. They may be charged with involuntary manslaughter in the deaths of the workers, officials said.
The workers were employed by contractors to Caltrans.
The Associated Press contributed to this report.