The storms hit on Easter Sunday as residents across the U.S. South, like most Americans, were under strict "stay-at-home" orders by the governors of Mississippi and Louisiana due to the nationwide coronavirus pandemic.
All six fatalities were recorded in Mississippi, the state's emergency management agency said on Twitter, and tornado warnings remained in place across several counties into the evening.
The National Weather Service said 13 tornadoes were believed to have touched down across the region.
Images on local media showed the devastation left behind by twisters, including destroyed homes, downed power lines, twisted billboards and overturned cars.
The city of Monroe, Louisiana, posted photos of wrecked buildings on social media and said that Monroe Regional Airport had canceled all flights until further notice due to debris on the runway and weather conditions.
"By the grace of God, early reports show only a few minor injuries. Pray for our city! Many neighbors & friends suffered catastrophic damage," Monroe Mayor Jamie Mayo said on Twitter.
Tornado warnings were also issued for parts of Texas into Sunday night.