The flights cancelled by 8 pm GMT on Sunday included over 2,400 entering, departing from or within the United States, according to tracking website FlightAware.com. Globally, more than 11,200 flights were delayed.
Among the airlines with most cancellations were SkyWest and SouthWest, with 510 and 419 cancellations respectively, FlightAware showed.
The Christmas and New Year holidays are typically a peak time for air travel, but the rapid spread of the highly transmissible Omicron variant has led to a sharp increase in COVID-19 infections, forcing airlines to cancel flights as pilots and cabin crew quarantine.
Transportation agencies across the United States were also suspending or reducing services due to coronavirus-related staff shortages.
Omicron has brought record case counts and dampened New Year festivities around much of the world.
The rise in US COVID cases had caused some companies to change plans to increase the number of employees working from their offices from Monday.
US authorities registered at least 346,869 new coronavirus on Saturday, according to a Reuters tally. The US death toll from COVID-19 rose by at least 377 to 828,562.
US airline cabin crew, pilots and support staff were reluctant to work overtime during the holidays, despite offers of hefty financial incentives. Many feared contracting COVID-19 and did not welcome the prospect of dealing with unruly passengers, some airline unions said.
In the months preceding the holidays, airlines were wooing employees to ensure solid staffing, after furloughing or laying off thousands over the last 18 months as the pandemic hobbled the industry.