Firefighters found the structure engulfed in flames shortly before midnight, and called for additional help.
In all, 15 fire departments and 150 full-time and volunteer firefighters fought the blaze.
Despite flames soaring to 30 feet, no injuries were reported. The fire was the largest in Warrenton in a decade.
The store is a total loss.
On Monday, firefighters were working to put out hot spots so the fire doesn't re-ignite and so investigators can poke through the debris on Tuesday. They suspect arson.
According to Chief Kenny Clayton of the Warrenton Volunteer Fire Department, many questions remain, including details about a fire that broke out several hours earlier in the store.
About 7 p.m. a fire was discovered in the paper goods section, but the manager was able to extinguish that blaze.
Fire investigators hope the building will be cool enough to enter Tuesday, when they will be joined by an SBI team.
There have been several other cases of arson in the area, but none of those is so far suspected of being related to the Lowe's fire.
The supermarket being destroyed is bad news in the rural town, especially for senior citizens like Rebecca Royster with no access to transportation.
The only other large-scale supermarket is 10 to 15 minutes up the road.
"I had no way up there unless I pay a cab, and I can't afford that unless I can get someone to take me," Royster said.
Lowes Supermarkets said it is too pre-mature to say if they are going to re-open the store.
Most of the side stores in the strip mall will open Tuesday.
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