The number of bodies recovered was not specified. Rescue efforts are under way and continuing overnight.
Footage uploaded to social media shows floodwaters causing chaos, knocking down bridges and dragging cars through the streets. Other video appeared to show people clinging to trees to avoid being swept away.
Radio and TV stations have reportedly been receiving hundreds of calls for help from people trapped in flooded areas or searching for loved ones, as emergency services struggle to reach some areas.
Emergency services workers are using drones to search for the missing in the badly affected municipality of Letur, local official Milagros Tolon told Spanish public television station TVE.
“The priority is to find these people,” she said.
Spain’s state weather agency AEMET has declared a red alert in the Valencia region and the second-highest level of alert in parts of Andalusia.
Valencia city hall said all schools and sporting events are suspended on Wednesday, and parks will stay closed.
Spanish Prime Minister Pedro Sanchez said in a post on X he was following reports of missing people “with concern”.
He urged people to follow the advice of the authorities, adding that people should “avoid unnecessary trips.