The Xylella fastidiosa bacteria also threatens citrus fruit and vineyards.
The Commission says at least 10% of the 11 million olive trees in Lecce are infected. It wants Italy to destroy infected trees and restrict any trade in species vulnerable to the disease.
New emergency measures are to be proposed by the Commission this week.
Thousands of hectares of olives are affected by the outbreak - a major worry for Italy, which is the EU's second biggest olive oil producer after Spain.
The Commission set out a range of measures to contain the outbreak last July, but says the situation has deteriorated since then and more action is needed.
The European Food Safety Authority (EFSA) says the disease, which kills trees by desiccation, is spread by various sap-sucking insects.
An EFSA spokesperson told the BBC that there remain "a lot of uncertainties" about the Italian outbreak, despite a comprehensive EFSA study of it published in January.
"Even trees not showing symptoms might carry the bacteria, which makes it really difficult. Just cutting down trees with symptoms might not be enough," he said.
Italian officials in Lecce say 15km-wide (nine-mile) buffer strips will be created around plantations which have infected trees. Those strips should be free of species vulnerable to the disease, so that the blight is contained.
Local officials, quoted by Italy's AGI news agency, suspect the disease entered Italy through ornamental plants imported from Costa Rica.
The Xylella blight has previously ravaged vineyards in California and citrus groves in Brazil, EFSA says.
A local campaign group called Peacelink disputes the EU data on the disease, however, arguing that a fungal infection is most likely to blame.
In a letter to EU Health and Food Safety Commissioner Vytenis Andriukaitis, Peacelink says more than 500 olive trees treated for fungi have recovered since spring last year.
It says research by the University of Foggia pointed to fungi, rather than Xylella, as the cause.
Peacelink urged the EU not to destroy olive trees en masse in the affected area, saying such a move would be "totally unnecessary".

Fjelde, 22, recently left Byrne in his native Norway and his move is subject to international clearance.
Scottish forward Loy, 28, was previously loaned to St Mirren by Rangers in 2010.
The Buddies - bottom of the Scottish Championship - visit Dunfermline Athletic on Saturday.
Former Viking Stavanger player Fjelde told St Mirren's website: "It's a big challenge ahead but I'm looking forward to it and hopefully together we can stay up. It's always been my dream to play in the UK."
And ex-Falkirk forward Loy, who has 58 career goals, said: "I've played in this division for two years and did very well in it so I'm not sure it's a case of having anything to prove. I want to score goals and I want to help keep the club up."
Italy must step up efforts to contain a bacterial disease blighting olive trees in the southern province of Lecce, the European Commission has warned.
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St Mirren have signed midfielder Pal Fjelde and striker Rory Loy until the end of the season, with the latter joining on loan from Dundee.