COVID-19 cases among airline staff plus poor weather conditions resulted in 2,581 nationwide flight cancellations as of 4 p.m. on Saturday, according to Flight Aware.
The news comes after a week of mass flight cancellations, pushing the total number of flight cancellations this week to over 12,000.
The number of flights canceled on Saturday was the largest in a single day this week.
Airlines, which have been canceling hundreds of flights every day since Christmas Eve, canceled the largest number of flights on Saturday. On New Year's Eve, there were 1,625 flights canceled.
The Federal Aviation Administration issued a warning to travelers on Friday that flight cancellations will continue as it experiences staffing issues.
Southwest Airlines said it has canceled 473 New Year's Day flights. The company announced it will suspend operations at its Chicago Midway hub on Saturday as of 1 p.m. CST due to weather.
"Our Planners proactively suspended operations at both Chicago airports as of 1pm CST today (we operate well more than 200 departures a day at Chicago Midway) anticipating the gusty winds and blowing snow that decades of our history operating in this airport show us will slow down the airspace and also make deicing and getting aircraft back into the air very challenging," Southwest said to ABC News in a statement.
"No doubt, for passengers of all air carriers, Chicago travel will be tough today," Southwest Airlines said.
Delta Airlines said it had canceled 196 flights on Saturday.
"A combination of issues, including but not limited to inclement weather in some areas of the country and the impact of the omicron variant, are driving cancellations," the airline said on its website.
American Airlines said it canceled 207 flights on Saturday.
"The winter storm in Chicago is having an impact on our operations, accounting for a significant number of our mainline cancellations," American said in a statement to ABC News. "t’s affecting both flights in and out of Chicago and other flight sequences for our crew. The number of COVID-related sick calls is consistent with what we have seen over the past few days. The vast majority of impacted flights were precanceled yesterday so we could proactively notify and accommodate our customers and avoid last-minute disruptions at the airport ."
American Airlines also said that it had "issued a travel notice to allow all customers whose travel plans are impacted by the Chicago storm to rebook without change fees. We apologize to our customers whose travel plans have been affected, and want thank to our team who have worked tirelessly to help us care for our customers."
Skywest Airlines said it canceled 465 flights Saturday.
"We continue to experience the impact of weather and the omicron variant across several SkyWest hubs, and have proactively canceled a significant number of flights due to the weekend’s weather in Chicago, Denver, and Detroit," Skywest Airlines said in a statement to ABC News.
Skywest also said that its teams "are working nonstop to minimize impact to customers and crew. Customers should check their carrier’s website or app for the latest information about their flight."