SDPD homicide detectives said just after 2 a.m. a group of people were seen fighting in the 400 block of G Street, near 4th Avenue.
When an officer approached them, the group ran off, but a man was discovered lying unconscious in the middle of the street. That man was rushed to a nearby hospital and was said to be in critical condition.
Witnesses said they heard homicide detectives later in the morning describe the victim to be "brain dead."
During the investigation, G Street and 4th Avenue were closed off to traffic and detectives were seen talking to nearby businesses.
The victim is only described as a man in his 20s.
A motive is not known for the attack. Detectives are looking for a person of interest described as a 25- to 30-year-old white man, 5-5-feet, 9-inches, 165 pounds, and last seen wearing gray slacks and a gray suit jacket.
If anyone has any information that might help police, they are urged to call Crime Stoppers at 888-580-8477.