The killing of a commander in the Revolutionary Guards Corps at the hands of ISIS also highlights the extent of Iranian involvement in Syria and the dire straits in which Assad finds himself, Washington-based analysts say.
Brig. Gen. Hossein Hamedani was killed outside Aleppo, Syria, where he was advising the Syrian army in its fight against extremists, Iranian state media reported Friday.
Iranian media carried messages of condolence from Iranian President Hassan Rouhani, who described Hamedani's death as a big loss and applauded the senior commander for his bravery.
"He was in charge of [Iranian] operations inside Syria," said former CIA officer Reuel Marc Gerecht. "He's been involved in this from A to Z, so in the short term, it's probably a fairly significant loss."
The current U.S. intelligence official said the general's death would be a setback for fighters supporting the government.
"There's no doubt that it is a psychological blow to pro-regime forces in Syria," he said.
Analysts say the high-level loss highlights the extent of Iran's involvement in the fighting.
"The fact that you have a senior Iranian general shows both the desperation of the regime, as well as now the degree of Iranian involvement now in Syria," said Andrew Tabler of the Washington Institute for Near East Policy.
The United States and Iran both say they are fighting ISIS terrorists, but in practice they have different goals: The United States is supporting rebels trying to oust Assad, while Assad's close ally Iran became involved to defend his regime.
"I'm not sure it's the Iranian objective to beat ISIS," said Gerecht. "I think the primary Iranian objective is to ensure that Assad does not fall."
Iran has become increasingly public about its aid to Syria's government, at first not disclosing flights to Syria in 2012 which Washington believed to be full of advisers and weapons. Now, however, Iranian officials praise their officers for assisting and advising Syrian regime forces.
"It's harder for the Iranians to hide when it's someone like that who has real visibility," said Dennis Ross, former adviser on Iran to President Barack Obama.
In an interview with Iranian TV last weekend, Assad publicly thanked the Iranians -- along with Russia, which last week began bombing his opponents -- for their support.
"We want help from our friends, and this is what Iran is offering, and what Russia is offering," he said, hailing Russia's recent initiative to form a coalition between Russia, Syria and Iran.
During the summer, the commander of Iran's elite Quds force, Gen. Qasem Soleimani, traveled to Moscow.
Tabler says he believes Iran was instrumental in bringing Russia into a coalition to come to the regime's aid -- and planning a two-tiered military comeback campaign to do it.
"Iran and their Shia militias, and Hezbollah, are the ground component to Russia's air involvement," he said.
"While most attention seems to have been focused on Russian intervention in the last week or so in Syria," he continued, "actually it is combined with a giant Iranian offensive that was planned months ago with the Russians -- and that is unfolding."
But the involvement is not cost-free for Iran.
"The losses for the Guard Corps are increasing," said Gerecht. "We see the funeral announcements all the time of (Iran Revolutionary) Guard members who are perishing in Syria."
In addition, U.S. officials told CNN on Thursday that four missiles Russia had aimed into Syria landed in Iran instead, resulting in some destruction of property and possibly civilian casualties. Russia and Iran both denied the reports, but any such "friendly fire" would complicate Russia and Iran's partnership.
The U.S. intelligence official noted the cost to Iran in continuing its support of Damascus, raising the question of how much in resources Iran will be willing to devote to its Syrian operations.
"Though it appears that Tehran is committed to doubling down on supporting the Syrian regime, its expanding role in the conflict will put more Iranian lives at risk to support a failed dictator," he said.