The fire was first reported at about 3 a.m. in the 10800 block of Carls Road in unincorporated Marengo.
Firefighters said a barn measuring approximately 150 by 80 feet was engulfed in flames.
One person was taken to the hospital, but officials said the medical emergency was not related to the fire.
However, three horses and a pony were unable to escape the barn and died.
There were no injuries among firefighters.
Marengo fire officials said firefighters relied on water tenders to shuttle water from a hydrant that was about 3.5 miles away.
The fire is not believed to be suspicious in nature, but it remains under investigation.