Gwent Police are appealing for witnesses after a report of a road traffic collision on the Prince of Wales Bridge at around 4pm on Thursday 2 March.
Officers attended, along with personnel from the Welsh Ambulance Service and the Welsh Air Ambulance.
The collision involved three cars and a van: a Land Rover, a Volkswagen ID3, a Volkswagen Golf and a Ford Transit Custom van.
The driver of the Volkswagen ID3, a 53-year-old man from Brighton and the passenger, an 82-year-old woman from East Sussex, were taken to hospital with serious injuries.
The driver of the Land Rover, a 30-year-old woman from Wiltshire, has been arrested under suspicion of causing serious injury by dangerous driving and remains in police custody.
Police asking for anyone who may have witnessed the collision, or any motorists with dashcam footage, that were using the M4 Prince of Wales Bridge between 3.50pm and 4.15pm to contact them.
You can call Gwent Police on 101 or send them a direct message on Facebook or Twitter, quoting log reference 2300069186 with any details.
Alternatively, you can call Crimestoppers anonymously on 0800 555 111.
