The shooting was reported just after 7 p.m. near the La Cienega/Jefferson station in West Adams.
LAPD Capt. Jamie Bennett said there appeared to be an argument on the street level of the station, which continued on the train, where a shooting happened.
"The men that we believe were responsible left the platform running down the staircase," Bennett said.
Responding officers found the victim dead when they arrived at the scene. The man was believed to be around 35 years old.
The suspects were only described as three men on skateboards.
A motive for the shooting remains under investigation.
Service on the E Line was halted.
"Violence on the streets that spills over onto our public transit systems is an increasing issue in the Greater Los Angeles area," Metro said in a statement. "Metro extends its condolences to the family and friends of the victim's family. The Los Angeles Police Department is leading the investigation."
The shooting happens amid rising concern over violence on Metro trains and buses.
In recent weeks, there have been incidents including an attack on a bus driver, a stabbing on a bus in Lynwood and a fatal shooting on a bus in Commerce.
Police searching for woman accused of attacking Metro bus driver in downtown LA
The Metro Board last month approved a pair of motions aimed at boosting safety on the system.