Thirty-nine people were killed when two car bomb explosions struck a pro-regime neighborhood in central Homs on Sunday, Syria's SANA news agency reported.
The London-based monitoring group Syrian Observatory for Human Rights gave the death toll as 46, with more than 100 people wounded.
Then on the southern outskirts of the Syrian capital, Damascus, three bombers struck in the Sayyidah Zaynab district Sunday, Syrian state media reported, citing security sources who said many casualties were feared.
ISIS claimed responsibility for the Sayyidah Zaynab and Homs attacks via the Telegram messaging app.
SOHR reported that the Damascus attacks were carried out via a suicide car bomb and by two suicide bombers.
Alawite neighborhood targeted in Homs
Homs Gov. Talal al-Barazi told Syria's SANA news agency that two cars packed with "huge amounts of explosives" were detonated near a bus stop in central Homs in the first attacks Sunday.
He said the initial death toll of 14 had risen as many of the wounded died from their injuries.
The blasts targeted students and government employees heading to work, the state-run TV station al Ikhbaria reported.
Firefighters spray water on a burning car at the bombing site in Homs.
Images from the site of the blast showed dozens of destroyed vehicles and severe damage to nearby buildings.
The bombings took place in the al-Zahraa district, a regime-controlled neighborhood that is predominantly home to members of Syrian President Bashar al-Assad's Alawite sect.
Al-Barazi said the attacks were aimed at the support base of the Syrian government, as the country's army made gains against rebels around the country.
Fourth bombing in neighborhood since December
The Homs neighborhood has been struck by three similar bombings in the past three months.
At least 24 people were killed and 100 injured in a coordinated car bombing and suicide bombing on January 26. Twin bombings also struck the neighborhood on December 28 and December 12.
ISIS claimed responsibility for all three previous attacks.
Syria's President open to ceasefire -- if it doesn't help 'terrorists'
Kerry: 'Closer to a ceasefire' than ever
Violence has continued to rage in recent days in spite of hopes to implement a "cessation of hostilities." More than a dozen countries agreed to the ceasefire at talks in Munich, Germany, earlier this month, but the agreement seems to have had little impact on the ground.
But at a press conference in Jordan on Sunday, U.S. Secretary of State John Kerry said a ceasefire was still "possible."
"We are closer to a ceasefire today than we have been, and I take nothing for granted about this," he told reporters at a joint press conference with Jordanian Foreign Minister Nasser Judeh.
Kerry had a telephone conversation with Russian Foreign Minister Sergey Lavrov on Sunday in which they "continued to discuss the modalities" of the truce, Russian state news agency Sputnik reported, citing the Russian Foreign Ministry.
Syria health care has collapsed, group says
More than 250,000 people have been killed, more than 1 million injured, and more than half of Syrians displaced since the country's civil war began in 2011, according to the United Nations.
CNN's Stefan Simons, Schams Elwazer, Elwyn Lopez, Mohammed Tawfeeq and Jomana Karadsheh contributed to this report.
