The family got into trouble just after 3.15pm when their boat capsized on the river, requiring a police helicopter to win them all to safety.
A man has been taken to Westmead Hospital in a critical but stable condition.
A five-year-old boy and a six-year-old girl were taken to the Westmead Children’s Hospital under stable conditions.
A 34-year-old man and a 27-year-old woman were taken to Nepean Hospital under stable conditions.
Police said early investigations suggest the river swelling may have played a role in the capsize.
The emergency operation comes only four days after a woman lost her life in the exact same place.