Appearing on NBC News' Meet the Press, Azar acknowledged that cases in the country have been rising as cold weather hampers "natural social distancing" from outdoor activities and suggested that Americans have grown "tired" of methods to mitigate the spread of the virus.
"The American people have given so much," Azar said. "We're seeing mitigation fatigue right now."
The United States added 57,519 new COVID-19 cases and 711 deaths Saturday for world-leading totals of 8,106,384 cases and 219,286 deaths since its first recorded case on Jan. 21, according to data collected by John's Hopkins University.
Azar encouraged Americans to continue following guidelines to prevent the spread of the virus while referring to "promise in the weeks and months ahead" of therapeutics and vaccines.
"Please -- my message to the American people, please practice those three W's. Wash your hands, watch your distance, wear your face coverings when you can't wear your distance. Stay out of settings where you can't do those things," he said.
He also warned Americans to be wary of attending indoor events or large gatherings, expressing regret over a campaign event for President Donald Trump in Florida last week where attendees were seen in close proximity to each other without masks.
"I wish everybody there would have worn face coverings and maintained social distance," Azar said.
Trump addressed rising cases in the country in a Twitter post Sunday, in which he repeated claims that the nation's high case total is a result of testing.
"No country in the world tests at this level. The more you TEST, the more CASES you will be reporting. Very simple!" Trump wrote.
Twitter on Sunday removed a post by White House coronavirus task force member Dr. Scott Atlas seeking to undermine the effectiveness of wearing masks and other face coverings to prevent the spread of COVID-19.
"Masks work? NO" Atlas wrote in the tweet followed by claims misrepresenting the science behind the effectiveness of masks, which Twitter deemed violated its Misleading Information Policy, which prohibits sharing false or misleading content related to COVID-19 that could result in harm.
Adm. Brett Giroir, assistant secretary for health and the Department of Health and Human Services and coordinator for the Trump administration's testing response, later seemed to counter Atlas' tweet writing, "#Masks work? YES!"
"And even though cases/hospitalizations are increasing, we can control #COVID19 by wearing masks when we can't distance, avoiding crowds especially indoors, good hygiene and smart testing of contacts and to identify/isolate those asymptomatic but infectious," Giroir added.
The National Governors Association sent a list of questions to the Trump administration seeking to clarify how to most effectively distribute and administer a COVID-19 vaccine, including how vaccines will be allocated to states, who determines how many doses each state will receive, who will pay for the vaccine and related personnel costs and whether there is a national strategy to prioritize what states will receive vaccines when supply runs short.
"How is this going to work? We need to answer these questions before the vaccine is available so that we are ready to go and no one is caught flat-footed when the time comes to vaccinate people," said New York Gov. Andrew Cuomo, who chairs the bipartisan association of the nation's governors.
California, which leads the nation in cases, added 2,862 on Sunday bringing its total to 867,317, while also reporting 44 new deaths for the nation's third-highest death toll at 16,943.
Texas is second in cases adding 3,048 new positive cases for a total of 823,779 as its death toll rose by 30 to 17,014, second behind New York.
Third-place Florida reported 2,539 new COVID-19 cases and 50 new deaths, bringing its total to 755,020 as well as the nation's fifth-highest death toll at 16,168. On Saturday, Florida reported 4,044 cases, the highest in two months.
New York reported 1,390 new cases for the nation's fourth-highest total at 484,281and added seven new deaths bringing its death total to 25,644 confirmed deaths. Including probable deaths, thw total is 33,357, according to Hopkins.
Cuomo on Sunday also announced that ski resorts in the state will be allowed to open at 50% capacity next month in order to "allow New Yorkers to have some outdoor activity this winter without having to quarantine when they come back."
Illinois reported 4,254 new COVID-19 cases for the nation's fifth-highest total at 344,048 cases after setting a single-day record for the state with 4,554 new cases on Friday. The state also added 22 new deaths, bringing its death toll to 9,214 -- seventh-highest in the nation.
Appearing on CNN's State of the Union Sunday, Illinois Gov. JB. Pritzker attributed the rising numbers to increased testing in the state as well as a "national wave" of COVID-19, while also sighting high positivity rates in its neighboring states of Iowa, Indiana and Wisconsin.
Pritzker added, however, that residents in the state have not been following mitigation measures, blaming Trump for modeling poor behavior.
"We are trying to get the word out. We're trying to convince people to do the right thing," he said. "But it is the president's allies in our state, all across our state, who are simply saying to people, 'Don't pay attention to the mitigations, don't follow the rules.'"