The A4 highway linking Madrid to Seville, the capital of the Andalucia region, was closed to traffic for over five hours because the Jabalon River overflowed its banks, a regional government official said.
Twenty secondary roads remained closed in the region, half of them near Cadiz, the interior ministry's traffic management agency said.
Snowfall also forced the closure of secondary roads in Asturias in the north, Salamanca in the centre and Girona in the northeast, it added.
The national weather office placed all of Andalucia on a "yellow" alert -- the second level on a scale of four -- which warns that meteorological conditions "are not unusual" but "potentially dangerous".
It predicted rainfall of up to 15 litres (3.9 gallons) per square metre (10.8 square feet) an hour in the region, accompanied by wind gusts of up to 80 kilometres (50 miles) an hour.