The United Nations on Tuesday suspended all aid convoys in Syria after an airstrike on aid trucks killed more than 20 people.
The Red Cross said civilians and at least one of its staff members died in the "horrific" attack northwest of Aleppo on Monday night, just hours after Syria's military announced a U.S.-Russia brokered cease-fire had failed.
"There can be no explanation or excuse, no reason or rationale for waging war on brave and selfless humanitarian workers," O'Brien said in a statement. "Let me be clear: If this callous attack is found to be a deliberate targeting of humanitarians, it would amount to a war crime."
Our thoughts go to families of brave @SYRedCrescent volunteers & staff killed in tonight's terrible attack on aid convoy in rural #Aleppo
"The perpetrators should know that they will one day be held accountable for violations of international humanitarian and human rights law," O'Brien added.
The cease-fire went into effect on Sept. 12 and called for a cessation in hostilities followed by the delivery of humanitarian aid. However, U.N. trucks with aid were stalled at the Turkish border as days passed.
Both the U.S. and Russia had expressed a desire to extend the fragile cease-fire, which saw guns fall mostly silent despite the issues in getting aid on the move.
The State Department said it was "outraged" by reports about the convoy and raised questions about the prospect of continued cooperation with Russia.
"The destination of this convoy was known to the Syrian regime and the Russian federation and yet these aid workers were killed in their attempt to provide relief to the Syrian people," spokesman John Kirby said in a statement. "Given the egregious violation of the Cessation of Hostilities we will reassess the future prospects for cooperation with Russia."
But U.S. Secretary of State John Kerry, speaking from a meeting of foreign ministers of 20 countries discussing Syria, told reporters: “The ceasefire is not dead.”
The International Syria Support Group (ISSG) released a statement saying member countries “agreed that, despite continued violence, there was still an imperative to pursue a nationwide cessation of hostilities based on the arrangement reached last week in Geneva between the United States and Russia.”
“They emphasized, in this context, the imperative of ending indiscriminate aerial bombardment of civilians, which is exploited by terrorist groups,” the statement said.
The attack has dealt a "devastating blow" to humanitarian operations in Syria, according to David Swanson, a spokesman for the U.N.'s Office for the Coordination of Humanitarian Affairs.
"The trucks, as per normal protocol, are always clearly marked and that's the most outrageous thing of this whole event," he told NBC News from Gaziantep, Turkey.
Swanson said the agency was trying to determine the precise cause of the attack to determine how best to proceed with its efforts.
"The situation in East Aleppo is particularly dire. There are between 250,000 and 275,000 people in urgent need ... As a result of what happened last night a lot of people are not going to be receiving the assistance they need," he said.
Cassandra Vinograd is a Senior Writer and News Editor. Before joining NBC News, she worked as a London-based correspondent for The Associated Press and specialized in politics, foreign affairs and defense.
Vinograd previously worked as an editor for The Wall Street Journal in Brussels and London.
She has reported extensively from Afghanistan and on West Africa and the Middle East.
Alex Holmes, Aggelos Petropoulos, Gabe Joselow and Matthew Grimson contributed.