At least 30 people have been killed in a double blast near the Shia shrine of Sayyida Zeinab, south of Damascus, Syrian state media say.
Dozens of people were also reported to have been wounded.
The shrine, which is highly revered by Shia Muslims, has been targeted before, most recently in February last year.
The attacks came as delegates from the Syrian government and opposition groups gathered in Geneva for tentative UN-sponsored peace talks.
The main opposition group backed down from its threat to boycott the talks. but says the Syrian government must meet its demands if negotiations are to start.
Syrian state media say the first blast near Sayyida Zeinab was caused by a car bomb. The cause of the second explosion was not made clear.
The shrine contains the grave of one of the Prophet Muhammad’s grand-daughters, and many Shia pilgrims have made the journey to visit it despite the civil war.
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.
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.