It occurred between December 1675 and August 1676, and resulted in approximately 11,300 deaths, making it the deadliest epidemic in Maltese history.

The exact cause of the outbreak remains uncertain, but infected merchandise from North Africa seems to be a likely source since the disease first appeared in the household of a merchant who had received goods from Tripoli.

The epidemic spread rapidly and efforts to contain it were poor, in part due to disagreements on whether the disease was actually plague or not.

Being surrounded by sea made it quite easy for such diseases to spread, as people at the time were making money through fishing and merchant trading.

[5] She had been examined by the doctor Giacomo Cassia,[5] who informed the protomedicus Domenico Sciberras of the case, but they did not identify the disease as the plague.

[2] Ġan Franġisk Bonamico, who survived the plague, wrote that it entered the island in a cargo of textiles from Tripoli which was delivered to Bonnici.

[5] Members of the Agius family, relatives of the Bonnicis, also became ill and died, and this raised alarm and the authorities closed the houses of the victims.

[5] Further cases appeared in the next few days, and on 28 January the health authorities held a secret meeting and concluded that the disease was probably the plague.

Attempts to contain the epidemic began immediately and all suspected cases were isolated, but the disease continued to spread rapidly.

[8] The course of the epidemic was somewhat variable and it went through a number of ebbs and flows, and it spread extensively throughout the main island of Malta at its peak, particularly the densely populated urban area around the Grand Harbour.

Two Counts and a number of public health officials were also responsible for dealing with the outbreak and for carrying out the orders given to them by the four knights.

Residents of areas of Valletta with high infection rates, including the Manderaggio, Arċipierku and French Street, were forbidden to leave their homes and they were provided with food.

When the disease spread to the countryside, the entire island was declared as infected, and international quarantine measures were adopted.

[1] People were forbidden to gather in churches and hotels and in outdoor public spaces, barricades were built and isolation hospitals were enlarged once again.

The Order's fleet was anchored in open sea at night, and a temporary accommodation was built at Marsamxett for patients.

[6] On 27 April, Grand Master Cotoner and the Council of the Order requested assistance from abroad to help deal with the epidemic.

Confirmed and suspected cases at Fort Saint Elmo were transferred to the Isolotto, and a general curfew was proclaimed on 25 May.

[6] By mid-April, the Capitano della Verga of Mdina had closed the city and successfully managed to prevent the epidemic from reaching its population.

[6] On 14 June, it was concluded that there were enough medical supplies on Malta, and the restrictions placed on certain areas of Valletta were lifted two days later.

[8] On 24 September 1676, the end of the epidemic was celebrated with the clearing of barricades, firing of guns, ringing of bells and processions.

Before the epidemic, mourning periods would last for one or two years, and three days after a person died no fire would be lit in the kitchen in the house of the deceased.

[2] In 1677, Laurentius Haseiah (or Hasciac) published De postrema Melitensi lue praxis historica in Palermo.