EasyJet cancelled 62 flights scheduled for Monday, after axing at least 222 flights across Saturday and Sunday.
Some holidaymakers reported being stuck abroad with no explanation or alternative route home offered by the airline.
A spokesman for the airline said: “As a result of the current high rates of Covid infections across Europe, like all businesses easyJet is experiencing higher than usual levels of employee sickness.”
The airline attempted to limit the impact on passengers by focusing cancellations on routes with multiple daily flights.
The spokesman added that the number of cancellations “represents a small proportion” of the total of 1,645 planned for Monday.
British Airways cancelled at least 115 flights to or from Heathrow Airport on Monday, although the PA news agency understands that only a handful were last-minute cancellations caused by coronavirus-related staff shortages.
It also suffered chaos on March 30 as flights were cancelled due to an IT meltdown.
The airline said: “Aviation has been one of the industries worst hit by the pandemic, and airlines and airports are experiencing the same issues rebuilding their operations while managing the continuing impact of Covid.”