The Saints made the announcement Friday, saying Payton will not be on the sidelines for the matchup in Tampa. He was immediately isolated from the team, and will remain in isolation for 10 days unless he meats the league requirements for a fully vaccinated individual to return.
Defensive coordinator Dennis Allen will assume head coaching duties in his absence, the NFL said.
According to the team, Payton is fully vaccinated.
His positive test comes after he missed practice on Wednesday. The Saints said he was "under the weather" but had tested negative then. Payton was back at practices and meetings on Thursday.
This is the second time the 57-year-old coach has tested positive for the virus. Payton became the first known person in the NFL to test positive for COVID-19 in the beginning of the pandemic in March 2020.
His positive test comes as COVID-19 cases have spiked across the NFL – and across the country – in recent days due to the omicron variant.
Three Saints players — defensive end Cameron Jordan, running back Mark Ingram and receiver Ty Montgomery — did not play against the New York Jets on Sunday because of positive COVID-19 tests. But by Thursday, Jordan and Montgomery had been activated from New Orleans’ reserve/COVID-19 list.
Payton is expected to return for the team's next game against the Miami Dolphins on Dec. 27.
The Associated Press contributed to this report.