Two men, aged 47 and 60, died in the western city of Medina on Wednesday, an 84-year-old man died in Mecca and a fourth died in the Red Sea port of Jeddah.
All three cities are closely associated with the annual Muslim hajj pilgrimage, with commercial capital Jeddah being the main point of entry for pilgrims from overseas.
The fifth person to die was a woman, who succumbed in the capital Riyadh, the ministry's website reported.
It added that the total number of infections from Middle East Respiratory Syndrome coronavirus (MERS-CoV) in the Gulf nation was now 463.
MERS cases have also been reported in the United Arab Emirates, Jordan, Egypt, Lebanon and even the United States, with most involving people who had travelled to Saudi Arabia or worked there, often as medical staff.
The great majority of deaths from the virus have been in Saudi Arabia, however.
MERS is considered a deadlier but less-transmissible cousin of the SARS virus that erupted in Asia in 2003 and infected 8,273 people, nine percent of whom died.
There are no vaccines or antiviral treatments for MERS, a disease with a mortality rate of more than 40 percent that experts are still struggling to understand.
Like SARS, MERS appears to cause a lung infection, with patients suffering from a temperature, coughing and breathing difficulties.
But it differs in that it also causes rapid kidney failure.
Research has suggested that camels are the likely source of the virus.