File photo: U.S.-backed Syrian Democratic Forces (SDF) fighters stand guard in Raqqa, Syria, on Feb. 7, 2022. AP
Fresh fighting that erupted in eastern Syria's Deir Ezzor province in late August has left at least 23 civilians dead, Volker Turk said in a statement.
"The warning signs of a further fragmentation to the conflict in Syria are alarming," he said.
"We cannot afford to sit back and watch the country slide even deeper into an endless conflict, which has already scarred the lives of so many civilians."
The new fighting, which began on August 27, came after the US-backed Syrian Democratic Forces (SDF) detained Ahmad al-Khabil, head of the Deir Ezzor Military Council -- which is affiliated with the SDF.
The SDF had accused him of communicating with the Syrian government, and of alleged drug trafficking and mismanagement leading to a rise in Islamic State group activities.
Angry fighters loyal to Khabil launched attacks on the SDF that spiralled into clashes in several villages and towns, according to the Syrian Observatory for Human Rights.
The war monitor last week said 90 people had died in the violence, most of them fighters.
In addition to the 23 civilians killed, Turk said dozens of civilians had been arrested by the SDF for allegedly participating in the hostilities and thousands had been forced to flee their homes.
The attacks have affected civilians in camps for displaced people, markets, water treatment facilities and health centres, he said.
At the same time, "curfews and roadblocks have curtailed freedom of movement and driven food and fuel prices higher", he added.
As the conflict spilled from Deir Ezzor into Hassakeh and eastern rural Aleppo, it pulled in other armed groups, the statement said.
Turk expressed concern that the renewed "tensions and hostilities in and around Deir Ezzor will be exploited by other parties trying to exert their influence.
"All parties to this latest flare-up must end their fighting, and work to resolve their differences through dialogue to avoid opening another catastrophic dimension to the Syrian conflict."
Syria's war has killed more than 500,000 people, displaced millions and battered the country's infrastructure and industry.
The conflict has pulled in foreign powers and jihadists, and while the frontlines have mostly quietened in recent years, large parts of the country's north remain outside government control.