At least 50 people have died in blasts near the Shia shrine of Sayyida Zeinab, south of Syria's capital Damascus.
A bus station and a building housing military headquarters were hit by the blasts, which mangled nearby vehicles.
It happened as the government and opposition groups gathered in Geneva in a bid to start talks aimed at a political solution to the conflict.
The attack, claimed by the Islamic State group, was aimed at disrupting the talks, the EU said.
Both the Syrian government and opposition are in Geneva but the talks have yet to begin. The main opposition group says the government must first meet key humanitarian demands.
US Secretary of State John Kerry urged both sides to seize the opportunity to end the bloodshed.
Mr Kerry said there was "no military solution" to the spiralling crisis, which he warned could engulf the region if the tentative UN-sponsored negotiations fail as previous attempts have.
The UN envoy to Syria has scheduled separate discussions with both sides in Geneva on Monday.
The story of the conflict
Correspondents say the destruction is "huge"
A bus and building housing a military headquarters were hit by the
blasts
the scene said the air was thick with a sickly smell - a combination
of high explosives, blood and burnt fruit
Sunday's attacks near Sayyida Zeinab were carried out by two suicide bombers, but some witnesses spoke of three blasts.
TV footage showed burning buildings and destroyed vehicles. Scores of people were reported wounded.
The blasts took place several hundred metres from the golden-domed shrine, which was not itself damaged - although it has been previously targeted, most recently in February last year.
It contains the grave of one of the Prophet Muhammad's grand-daughters and continues to draw many Shia pilgrims, despite the civil war.
The destruction is huge. The building in front of me on Koua Soudan Street is charred black in the middle. I'm told that there is a military headquarters on the ground floor and families also lived in the five-storey building.
There is a fruit stall with blackened oranges all over the floor.
I can also see a large number of charred vehicles, including a bus in the middle of the street which is almost completely destroyed and overturned. The smoke is still rising from one of the cars on the side of the street.
BBC Arab affairs editor Sebastian Usher says Shia fighters from around the region have joined the conflict in Syria on the grounds that they wish to protect the shrine from the civil war.
The Lebanese Shia movement Hezbollah has cited it as a key reason that it chose to fight on the side of President Bashar al-Assad, he adds.
More than 250,000 people have died and 11 million have fled their homes in almost five years of civil war in Syria. The violence has also been the biggest driver behindEurope's migration crisis.
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