Residents in the coastal town of Seaford have been told to stay inside and keep their doors and windows closed, after people complained of stinging eyes and feeling sick due to a "sickly stink" in the air.
One of several people to contact Sussex Police described the smell as being "like burning plastic".
The force advised people to stay inside and said the noxious odour was first noticed in The Ridings area of town at around 6pm on Friday evening, but it failed to disperse.
They continued they are working with other agencies, including the coastguard, East Sussex Fire and Rescue Service and Lewes Council, to try to determine the cause of the smell.
In August, a toxic "haze" caused the evacuation of people from Beachy Head, which lies around eight miles along the coast from Seaford, chemical cloud enveloped part of the Sussex coastline.
Some 150 people required treatment for stinging eyes, sore throats and vomiting after the noxious haze rolled in from the sea, reaching the shore from Eastbourne to Birling Gap, near Beachy Head.
It is believed the most likely source of the fumes in the summer was a ship illegally flushing its tanks with chemicals.
Police do not think the two incidents are linked.