Officers responded to a report of an altercation between two groups of people in Hastings town centre, which was resolved peacefully.
Approximately 15-minutes after the groups had gone in separate directions officers received a report that a man from one of the groups had been stabbed outside ESK.
A 41-year-old man was taken to hospital with serious injuries.
The road was closed while investigating officers, including forensics, attended the scene to continue their enquiries.
There is likely to be an increased police presence in the area while enquiries continue.
A 26-year-old man has been arrested on suspicion of GBH, two counts of possession of an offensive weapon and possession of a Class A drug.
A 32-year-old man has been arrested on suspicion of GBH, wounding with intent, two different counts of possession of an offensive weapon and possession of a Class A and B drug.
A 44-year-old man has been arrested on suspicion of GBH, wounding with intent and possession of an offensive weapon.
Anyone with information or video footage which could help detectives with their investigation is asked to report it online or call 101 quoting serial number 186 of 03/09.