According to police and witnesses, a man was seen trying to cross the tracks under the moving train as the crossing lights and bells were activated and crossing arms were down.
Witnesses said the man walked onto the tracks at West Harbor Drive and West Market Street, and was hit by a Burlington Northern Santa Fe freight train.
"He was walking over the train tracks. I don't know if he was drinking alcohol. I've never seen anything like that, but there he is," said one witness, Oscar Frias.
San Diego police were first dispatched to the scene shortly after 11:30 p.m. Wednesday.
There is a possibility that video of the incident was captured on surveillance at nearby businesses, however police were not able to retrieve the video yet, because managers were not available at the time of the early-morning probe.
The case remains under investigation.