Fire officials in the city of Mason north of Cincinnati said the eighth-year pro and his family were out of town at the time.
Firefighters responded just after 2:30 a.m. Tuesday to what they describe as a very serious fire that collapsed the home's roof. They said hot spots and unstable areas are delaying their investigation into the cause.
Mason Deputy Fire Chief Craig Bryant said the house is a "total loss,' according to the Cincinnati Enquirer.
Bryant said firefighters remained on the scene Tuesday to investigate the cause and continue to control the fire, which continued to burn.
Odom and his family typically spend the offseason in Alabama, a neighbor told the Enquirer.
"We are in the process of reaching Antwan to express our concern," Bengals spokesman Jack Brennan said. "For just an expression of concern it's OK to contact him. There is no business-related contact with players during lockout, but for a personal matter such as this we are at least able to try to reach him."
The Warren County auditor's website estimates the home's value at nearly $1.2 million. It was built in 2000 and has nearly 6,000 square feet of space.
The Associated Press contributed to this report.