It is unclear exactly how many cases are on the Grand Princess, which can carry nearly 4000 passengers and crew and is due to arrive in Melbourne on Thursday.
"Like many other tourism operators, we too have been impacted by the current fourth wave being experienced across Australia," a Princess Cruises spokesperson said in a statement.
Victorian Health Minister Mary-Anne Thomas said she expected any cases onboard to stay away from the rest of the community.
"That's the most important thing," she told reporters.
"We know now that there are many cases of COVID that are not being counted or reported."
About 95 per cent of guests on Princess Cruises vessels must be vaccinated, with the remaining five per cent of places allocated to those with medical exemptions.
Passengers with the virus are required to isolate for five days and their close contacts must have a test each day before leaving their cabin.
It comes as a new Australian study of 20,000 people confirmed that getting the virus increased a person's likelihood of developing blood clots, serious heart issues and other medical conditions requiring hospitalisation.
The research, led by Stacey Rowe from Monash University, showed that the risk was present not only when a person first became sick but could also last beyond the "acute" stage of their illness.
Information for the study was collected over the first 18 months of the pandemic, before anti-virals and vaccines became widely available.
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