Around 2:15 p.m., the Angelina County Sheriff's Department in east Texas received a call about a tree that fell on a car where two children aged 3- and 8-years-old were trapped in the back seat. A rescue team with the local fire departments were able to remove the kids, but they were pronounced deceased on the scene, police said.
Monroe County, Mississippi, Fire Coordinator Terry Tucker said two people had also died in Hamilton, Mississippi, but no further details were available. He said there were also multiple injuries and several damaged homes and businesses in the small town.
According to Alto Police Chief Jeremy Jackson, over two dozen injuries were reported and "a lot" of homes were flattened, ABC affiliate KTRE reported.
Flood alerts were also being issued for parts of the southern U.S. due to torrential rainfall that will continue overnight into Sunday.
There is a moderate risk for severe weather from Lufkin, Texas, to Jackson, Mississippi, including much of northern Louisiana. In the moderate risk region, dangerous, long-track tornadoes are possible. Additionally, destructive straight-line winds and very large hail are possible from eastern Texas to western Alabama.
Intense thunderstorms will continue through the overnight hours in parts of this region. There is a possibility of ongoing severe weather early Sunday morning, with night-time tornadoes and destructive winds.
On Sunday morning, storms will congeal into a line that will likely stretch from the Florida Panhandle to Ohio. The main threat will be straight-line, damaging winds. However, embedded tornadoes could develop in the line of thunderstorms.
The line of storms will impact the Appalachian Mountains on Sunday evening as they begin to lose their severe potential. Nonetheless, numerous severe thunderstorms, with damaging winds, large hail and a couple of tornadoes, are possible as the storms move through the region.
There is an enhanced risk for severe weather on Sunday from Georgia to Ohio, including Atlanta; Charlotte; and Charleston, West Virginia. Damaging winds, a few tornadoes and large hail are possible in the risk region.
In addition to the severe weather threat, storms will bring torrential rainfall over parts of Louisiana, Arkansas and Mississippi. Rainfall over 4 inches is possible in that region, which makes flash flooding a concern with the ongoing storms this weekend.
ABC News' Daniel Peck contributed to this report.