Emergency services were called to Barn Cottage Lane, Haywards Heath, following reports a man had been stabbed at about 8.20pm.
Police say the man, 29, sadly died on his way to hospital.
Then on Saturday (December 22), armed officers and police dogs descended on a neighbourhood in the area of the stabbing at about 11.30am.
A 51-year-old and a 21-year-old, both from Haywards Heath, were arrested on suspicion of murder, said police. They both remain in custody.
Detective Superintendent Tanya Jones said: "We believe the victim had been cycling on his bike at the junction of Barn Cottage Lane and Bentswood Crescent when he was attacked by, what we believe to have been, two men.
"We believe this was a targeted incident and the victim and his attackers are known to each other.
"We are appealing to anyone who saw what happened or has any information to please contact us. We have spoken to a number of witnesses but we are keen to speak to more people who might have information.
"We currently have officers in the town trying to trace further people who may have been involved.
"I would urge anyone who witnessed the incident, the events leading up to it or who has any information to assist our enquiry to report online or call 101 quoting Operation Trevally."