Brittany Ferries is to stop its Portsmouth to St Malo crossings from next month.
Since the weekend, 35,000 people have cancelled their bookings because of quarantine.
The company said its ferries will also not be travelling to Spain, as demand for sailings this autumn is "extremely weak".
The decision comes after the holiday-makers coming back from France are now required to quarantine when they return to the UK.
Christophe Mathieu, director general Brittany Ferries said: "This is not something we want to do."
"These extraordinary decisions are regrettable and we apologise in advance to all those whose travel plans will be disrupted.”
Around 50,000 passengers with existing bookings are said to be affected by the schedule changes.
Passengers are being asked to wait and see if any changes are made to their bookings before contacting the company.