Elizabeth Harpley, 36, and her sons – Mathew Harpley, 10, Christopher Harpley, nine, and Mitchell Devine-Harpley, five – were last seen at Koshigaya Park, Campbelltown about 2pm on Sunday.
Family and police have serious concerns for their welfare as the children live with conditions that require medication, which they do not have with them.
They may be travelling with a man, 49, who is known to the family, and may be travelling in a red Jeep with Queensland registration plates 061 VKM, police said.
Elizabeth is described as being of Caucasian appearance, with medium-length brown hair. She is heavily pregnant and was last seen wearing jeans, a black t-shirt and a cardigan.
Mathew is described as being of Caucasian appearance, with a slim build and short, blonde, curly hair. He was last seen wearing blue jeans and a dark green hooded jumper.
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Christopher is described as being of Caucasian appearance, with a slim build and short, brown, curly hair. He was last seen wearing blue jeans with a brown hooded jumper.
Mitchell is described as being of Caucasian appearance, with slim build and short, blonde, wavy hair. He was last seen wearing dark blue jeans and a yellow t-shirt.
They are known to frequent the areas of Campbelltown and Wollongong in NSW, and Pullenvale in QLD.
Anyone who sees the children should call triple zero immediately.