The bloodshed came a day after another 31 civilians were killed in Eastern Ghouta and as the United Nations pleaded for a truce in the seven-year-old conflict to allow for aid deliveries.
Fighting also raged in the northwestern province of Idlib, where the UN said the violence "made a mockery" of the de-escalation zones agreed last year in a bid to pave the way for an end to the war.
The latest casualties in Ghouta, on paper also a de- escalation zone, came as Washington threatened military action over the reported use of chemical weapons in the enclave, which regime and allied forces have besieged since 2013.
Observatory chief Rami Abdel Rahman added that few rebels were among the dead because they rarely left their tunnels and had better protection from air strikes than civilians, estimated to number around 400,000 in Ghouta.
In apparent retaliation, rockets were fired on Damascus's Bab al-Touma neighbourhood, killing three civilians, the state news agency SANA reported.
Although less deadly, regime attacks involving suspected chlorine-filled munitions on Ghouta have also been on the up in recent weeks.
Washington, which last year launched cruise missiles on a regime airfield in retaliation for a nerve agent attack in Khan Sheikhun that killed scores of people, has threatened more military action.
France last month blacklisted companies and nationals it said had links to Syria's alleged chemical programme.
US ambassador to the UN Nikki Haley clashed with her Russian counterpart at a meeting of the Security Council on Monday after proposing a statement condemning Damascus "in the strongest terms".
Russia, Assad's main backer, retorted that "no perpetrators have been identified" and accused the United States of orchestrating a "propaganda campaign" against the Syrian government.
"Over the last 48 hours, the scale and ferocity of attacks has increased dramatically," the UN-mandated Independent International Commission of Inquiry said in a statement.
In Idlib, the last province in the country to largely escape government control, daily fighting is also claiming an growing human toll and displacing thousands.
The UN commission said at least three hospitals were hit in recent strikes and shelling.
"These reports are extremely troubling, and make a mockery of the so-called 'de-escalation zones' intended to protect civilians from such bombardment," said Paulo Pinheiro, chair of the Commission.
The measure would "enable the delivery of humanitarian aid and services, evacuation of the critically sick and wounded, and alleviation of people's suffering, to the extent possible, wherever they are," the UN said.
The UN said existing agreements on the delivery of aid were not being honoured and stressed that "if access was granted, three convoys could be dispatched each week, reaching over 700,000 people in these areas in two months."
There was no immediate comment from the regime or any of the other belligerents on the UN's appeal.
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