Most flights between Europe and North America are being diverted because of the ash cloud's latest drifting, officials at Eurocontrol, the agency that co-ordinates aviation safety in Europe, said.
Flights are being rerouted north and south of the 2,000km long cloud.
The Spanish national airport management agency (Aena) said the airports affected were Barcelona, Girona, Sabadell, Bilbao, San Sebastian, Vitoria, Zaragoza, Huesca, Pamplona, Logrono, Santiago, La Coruna, Vigo, Asturias, Santander, Leon, Valladolid, Burgos and Salamanca.
Airspace across Europe was closed down for up to a week last month after the eruption of Iceland's Eyjafjallajokull volcano, but was reopened after emergency talks between European governments, airlines and regulators.
Eurocontrol warned on Saturday of a rise in emissions from the volcano.
"The area of potential ash contamination is expanding in particular between the ground and 20,000 feet," it said.
Eurocontrol said airports were also expected to close in northern Portugal and parts of southern France.
"Logically, we will be spared until Monday noon, based on current forecasts," a French aviation authority spokesman said.
Brian Flynn, the deputy head of operations at Eurocontrol, told Al Jazeera that there is a "slight risk that there could be a further spread to the south of France".
"We hope that this incident won't be quite as devastating as last time. However, that depends on the spread of the ash cloud because there is a very extensive area over the north Atlantic if the winds change, there will be very significant closures in Europe today," Flynn said.
In the UK, some flights to Spain were being affected.
At London Stansted, 22 Ryanair flights to the Canary Islands, mainland Spain and Portugal were cancelled, along with three EasyJet flights.
Flights from Gatwick to Portugal, Alicante and Madrid were cancelled and at Heathrow some flights to La Coruna in northern Spain were also grounded.
Flights across Ireland and parts of the UK were disruptedearlier this week.
The international airline industry body, IATA, said last month's shutdown had cost airlines about $1.7bn and called on governments to pick up at least part of the cost.
Eurocontrol said more than 100,000 flights to, from and within Europe had been cancelled between April 15 and 21, preventing an estimated 10 million passengers from travelling.