Three apparently coordinated suicide attacks on Monday targeted Medina, the US consulate in Jeddah and the largely Shia Muslim city of Qatif on Monday. At least four security officers were killed.
No group has claimed responsibility but Islamic State has carried out similar bombings in the US-allied kingdom in the past year, targeting Shias and Saudi security forces.
Zeid Ra'ad al-Hussein, the UN High Commissioner for Human Rights and a member of the Jordanian royal family, delivered his remarks via a spokesman in Geneva.
"This is one of the holiest sites in Islam, and for such an attack to take place there, during Ramadan, can be considered a direct attack on Muslims all across the world," he said, referring to the Islamic holy month.
"It is an attack on the religion itself."
Militant attacks on Medina are unprecedented. The city is home to the second-holiest site in Islam, a mosque built by the Prophet Mohammed, which also houses his tomb.
Attacks on Makkah, the most sacred place in Islam, have also been extremely rare. The Al Saud ruling family considers itself the protectors of both sites.
Islamic State says the Saudi rulers are apostates and has declared its intention to topple them.
Saudis were rattled by the rare, high-profile attack.