Two of the men, aged 57 and 71 from the town of Caldogno, have been in intensive care since being diagnosed with Weil's disease, a rare bacterial infection which attacks the kidneys and liver, Corriere del Veneto reported.
The pair are believed to have contracted the illness while out picking mushrooms last Tuesday.
Another man in his seventies, from nearby Sarego, was admitted to hospital on Wednesday, while another was admitted on Tuesday.
It is unclear how exactly they contracted the illness, but it is believed that at least one may have fallen in muddy water that was contaminated with rat urine while out mushroom picking.
The disease, also known as leptospirosis, can be transmitted through cuts and scratches or the lining of the mouth, throat or eyes, but it cannot be passed to another human being.
The two patients from Caldogno were taken to hospital last week, suffering from a high fever.
Marzia Miolo, the daughter of one of the men, told Corriere that her father was also struggling to breath after returning from the foraging trip.
She believes the disease was transmitted through a cut on one of his hands after it came into contact with the contaminated water. The fingers on the wounded hand were also swollen, she said.
Miolo, who is also the local president of Coldiretti, the farmers' association, said the friends had been searching for mushrooms - an extremely popular autumn pastime in Italy - in an area close to several abandoned houses that are swarming with rats.
It is unclear how her father's friend and the other two patients contracted the disease.
Miolo added: “I publicized the incident on Facebook. The area is frequented by children as well as mushroom pickers. It's important for people to be made aware of the risk.”
Marcello Vezzaro, the mayor of Caldogno, said a rodent control initiative is now underway but warned those out picking mushrooms to always wear protective gloves.
“It's a rare occurrence but we will do everything possible to ensure it doesn't happen again,” he said.
The disease, which usually begins with a high fever, manifests itself between two and 20 days from the moment it's contracted. It can be fatal if not diagnosed early.
The illness is extremely rare, with only one or two cases a year diagnosed in Italy, according to Raffaele Bonato, the head of San Bortolo's anaesthesiology and intensive care unit.
“It's unusual to have four serious cases at the same.”
In its mild form, the disease manifests itself with flu-like symptoms, but in severe cases its causes internal bleeding, organ failure and even death.
Around 10 million cases are diagnosed globally each year.