Several vehicles fell into the Tarn River north of Toulouse when the bridge near the village of Mirepoax-sur-Tarn fell around 08:00 (07:00 GMT).
Four people have been rescued and the river is still looking for others who may be missing.
An investigation into the causes of the incident has begun.
At least 60 emergency personnel have worked at the scene.
The bridge, 155 meters (170 yards wide) and nearly 7 meters wide, was renovated in 2003 by Hoyt-Garon Council.
The number of vehicles involved is contested but includes at least one truck, a passenger car and potentially a minibus.
Georges Merich, president of the regional council, said he would go to the site to be with the victims. , their loved ones and emergency services.