The incident happens as hundreds of thousands of Muslims are in the city to perform the Hajj pilgrimage.
According to the Saudi civil defense department, the incident occurred on Monday in a 15-story hotel.
Four Yemeni pilgrims have suffered minor injuries in the fire, state news agency SPA quoted the department as saying.
A preliminary probe has reportedly blamed the incident on a short circuit in a room, Press TV reported.
The incident comes after on Thursday about 1,000 Asian pilgrims were evacuated from another hotel in Mecca following a fire at the eighth floor of the place. Two Indonesian pilgrims were wounded.
The Hajj pilgrimage and performing all of its rituals is one of the central pillars of Islam. Every able-bodied Muslim who can afford it must make the pilgrimage at least once.
Earlier on September 11, a crane collapsed at the Grand Mosque of Mecca, killing over 100 people. Hundreds of people were also injured.