A 32-year-old man became ill and later died after being arrested by police in Haywards Heath.
The Independent Police Complaints Commission (IPCC) has launched an investigation.
Officers attended an incident in Ryecroft and approached a man leaving the area shortly before midnight on Saturday.
Officers restrained him and placed him in a police van where he became unwell.
He was removed from the van in South Road just after midnight and CPR was performed. He was subsequently transferred by ambulance to the Princess Royal where he died on Tuesday.
The man has not been named. His family has been informed.
Sussex Police made a mandatory referral to the IPCC who declared an independent investigation on Sunday. As part of the investigation, the IPCC has examined the scene and initial statements from the officers involved have been gathered. On Tuesday they made house-to-house enquiries and spoke to witnesses.
IPCC Commissioner Jennifer Izekor said: “Following this incident a 32-year-old man tragically lost his life and my thoughts are with his family and friends at th is time. The IPCC will carry out a robust and thorough investigation.”
A post-mortem has yet to be conducted.
Anyone wishing to give their tributes can call 01444 419583.
The witness appeal number is 0800 015 4877 or email: firstname.lastname@example.org