"To my sorrow and sadness, I have received news of the earthquake in Bushehr Province and the human casualties and damages caused by it," Ayatollah Khamenei said in a message on Tuesday.
Ayatollah Khamenei called on provincial and relevant officials to do their best to save the lives of the people and provide enough support to the survivors of the quake.
The Leader also called on the Iranian people to play their brilliant role to soothe the sufferings of the quake-stricken people.
An earthquake measuring 6.1 on the Richter scale jolted the town of Kaki in Bushehr province on Tuesday, killing at least 39 people and injuring more than 750 others.
The Seismological center of Bushehr province affiliated to the Geophysics Institute of Tehran University registered the quake at 16:22 hours local time (1152 GMT).
The epicenter of the quake was located in an area 51.5 degrees in longitude and 28.4 degrees in latitude.
Iran sits astride several major faults in the earth's crust, and is prone to frequent earthquakes, many of which have been devastating.
The worst in recent times hit Bam in southeastern Kerman province in December 2003, killing 31,000 people - about a quarter of its population - and destroying the city's ancient mud-built citadel.
The deadliest quake in the country was in June 1990 and measured 7.7 on the Richter scale. About 37,000 people were killed and more than 100,000 injured in the northwestern provinces of Gilan and Zanjan. It devastated 27 towns and about 1,870 villages.
In August 2012, two quakes in Northwestern Iran also claimed the lives of 306 people and injured more than 4500 others.
