Forty beds in eight wards have been affected, with four wards fully closed.
Visitors have been asked to stay away unless absolutely necessary. People suffering from sickness and diarrhoea have also been urged to call NHS Direct on 111, instead of visiting A&E.
It follows the closure of Bassett Green Primary School in the city on Friday because of a sickness bug.
Dr Sarah Schofield, of West Hampshire NHS Clinical Commissioning Group, said: The principals for any diarrhoea and vomiting illness is to have basic hygiene - be fanatical about your hand washing - and to drink plenty."
Infection control teams at the hospital were expected to reopen one of the closed wards on Sunday.
An outbreak of norovirus has led to the closure of several wards at Southampton General Hospital.