A serious accident near to the Royal Sussex Hospital closed Eastern Road.
Unconfirmed reports suggest a police car is involved in the crash, which happened at the junction with Chichester Place at about 4am.
At 8.30am, the road was still cordoned off in both directions. By 10.30am, traffic was flowing again.
Sean McLeod, whose girlfriend works nearby, said: “There’s been a bad accident – my girlfriend says a Sussex police car is wrapped around a tree. I hope the drivers are okay.
“A police car and another silver car were involved. The road is closed from Brighton College up until the occupational health building and there’s debris everywhere.”
The Brighton and Hove News understands there are only minor injuries involved.
The Independent Police Complaints Commission said they had been informed of the incident, but were not investigating at this stage.
A spokeswoman said: “We were notified of the incident by Sussex Police and are continuing to carry out an assessment of the available information to determine the level, if any, of IPCC involvement.”
Buses were diverted south and traffic was heavy throughout Kemp Town.
More follows.