He is thought to have had a cardiac arrest around the 16-mile mark of the course.
A Sussex Police spokesman said: "A 23-year-old man has sadly died after suffering a medical episode whilst competing in the Brighton marathon this morning.
"Emergency services were called to Grand Avenue in Hove at around 11.45am where it is believed the London man suffered a cardiac arrest.
He was treated at the scene by medical staff, including doctors and paramedics, along with an off-duty police officer, before being taken to hospital."
The man's family has been informed of his death.
A spokesman for organisers of the marathon said: "It is with regret that we can confirm that a competitor collapsed and later died competing in the Brighton Marathon this morning.
More top news
Thursday afternoon's weather for the west of the region
Thursday afternoon's weather for the east of the region
Border Force officers at Gatwick have prevented an attempt to smuggle approximately four kilos of cocaine into the UK.