The head of the main Syrian opposition bloc resigned after a nearly two-year term on Monday, two days before opposition groups and figures were set to meet in Riyadh ahead of UN peace talks in Geneva.
A statement from Riad Hijab did not say why he was quitting the Saudi-backed High Negotiations Committee, which includes both political and armed anti-government groups and has represented the opposition in previous peace talks.
However, the statement referred to attempts by foreign powers to carve up Syria into zones of influence "through side deals made without consulting the Syrian people", a reference to Russian-led ceasefire talks.
The start of three-day opposition talks in Riyadh on Wednesday is set to coincide with a meeting in the Russian city of Sochi between the presidents of rebel-backer Turkey and regime allies Russia and Iran to discuss violence reduction, boosting aid deliveries and finding a settlement to the conflict.
It comes as entire families have been buried under the rubble in a rebel-held enclave near Damascus, as government forces pursue a nearly week-long campaign against the area despite a deescalation deal.
The violence aims to further weaken rebels in their last stronghold near Damascus, analysts said, as Russia, Iran and Turkey launch a diplomatic dash to resolve Syria's grinding six-year conflict.
The three countries agreed earlier this year to establish deescalation zones aimed at reducing hostilities in four battleground areas across Syria.
One such zone came into effect in Eastern Ghouta in July, but after months of relative calm, intense artillery fire and air strikes have pummelled the region for the past week.
Residents of the opposition stronghold have described living in utter terror.
"We're forced to hide in parts of our home that aren't suitable for living, like the bathroom and the kitchen," said 28-year-old Majed.
"We even sleep there sometimes."
The father of two lives in Douma, one of the largest towns in Eastern Ghouta and a regular target of regime raids.
Despite his wife's efforts to create a normal life for their children, their four-year-old son has been left deeply scarred.
"When he hears the bombing, he runs to hide in the closet or behind the door, screaming, 'The plane, the plane is attacking'," Majed said.
Since Tuesday, government bombardment of Eastern Ghouta has killed at least 80 civilians, including 14 children, and wounded hundreds more, according to the Syrian Observatory for Human Rights, a Britain-based monitor.
In Douma on Sunday, doctors rushed to treat wailing children lying on bloodstained hospital beds.
Their eyes wide with fear, children awaited life-saving care, many having had limbs pierced by shrapnel.
Nearby, two men mourned over the lifeless body of a child, wrapped in a red-and-white sheet on the floor.
An estimated 400,000 people live in Eastern Ghouta, where a four-year government siege has made food, medicine, and other basic necessities either unavailable or too expensive.
Regime forces began their bomb assault there last week, after hardline rebel group Ahrar Al Sham attacked a military base in the nearby town of Harasta.
Rebel rocket fire on Damascus has also killed at least 16 people since Thursday, the Observatory said.
"Regime forces used the rebel offensive on Harasta as a pretext to target all of Eastern Ghouta," said Observatory head Rami Abdel Rahman.
He said government troops were trying to "turn the rebels' popular base against them".
Analysts say the Eastern Ghouta hostilities have marred the deescalation deal touted by the three countries meeting in Sochi on Wednesday.
Nawar Oliver of the Turkey-based Omran Centre think tank said the Eastern Ghouta zone "is not over, but it's hit a big obstacle".
"Obviously, the de-escalation deal in the Ghouta [area] isn't going too well," added Aron Lund, a fellow with The Century Foundation, a New York-based think tank.
Syria's government had long eyed Eastern Ghouta, viewing the enclave as "too close to the capital to be left like this", he said.
Rebels had "little chance" of surviving the assault, he added.
In the rebel-held town of Madira, near Douma, on Sunday, volunteers from the White Helmets rescue force climbed through the rubble of a building after a recent air strike.
Flashlights in hand, they scrambled over concrete blocks and metal rods to try to find the bodies of the family that had been living there.
"They're six people. We found three, and three are left," one volunteer said.
One volunteer dug into the rubble with a wooden stick and uncovered a limb, which he placed carefully in a white bag.
"It's a child's leg," his colleague said.
After regime shelling on Douma last week, paramedic Firas Al Kahhal said he had witnessed a haunting scene.
The 22-year-old was dispatched to the bombed-out home to search for any survivors.
"As soon as we entered I saw a baby girl, no more than eight months old, trying to crawl out of the rubble," Mr Al Kahhal said.
The infant had suffered wounds to her head, but survived.
"What we saw was heartbreaking. She lived under shelling and terror. Her brain can't even absorb what's happening."