A man has died shortly after he was placed in handcuffs on Saturday afternoon in Sydney's south-west.

Emergency services were called to a petrol station on the Cumberland Highway at Canley Vale at 3pm, after reports of concern about the man's behaviour.

Police allege the man assaulted the attending paramedics, and police were called.

Officers from Fairfield City Police Area Command restrained the man using handcuffs, before paramedics took him in an ambulance to Liverpool Hospital for assessment.

However, the man died at the hospital at 3.45pm.

It is believed the man was drug affected at the time.

Police were unable to say whether any force was used to restrain the man, due to the incident's status as a critical incident investigation.

A critical investigation team will now investigate all the circumstances surrounding the incident, which will be monitored by the independent Law Enforcement Conduct Commission.