Just a week after a Herculean effort by schools to reopen in line with last-minute Covid-19 rules, classrooms across the country will be shut to pupils and transformed into ballot stations for the two-day vote.
A triumph for the far-right in this fiercely fought campaign would sound alarm bells in Brussels.
It will be the first test for Prime Minister Giuseppe Conte's centre-left coalition government since it imposed an economically crippling nationwide lockdown to fight the virus, which has killed almost 36,000 people.
The referendum, on slashing the number of members of parliament — from 630 to 400 in the lower house, and 315 to 200 in the upper house — is expected to pass, though there has been a late uptick in the number of prominent 'no' declarations.
The cost-cutting reform is the brainchild of the co-governing Five Star Movement (M5S), but while its centre-left coalition Democratic Party (PD) partner and parties on the right are theoretically in favour, their support has been lacklustre at best.
The regional battle is for governance of Campania, Liguria, Marche, Puglia, Tuscany, Valle d'Aosta and Veneto.
The right-wing coalition is set to easily retake Veneto and Liguria, and it could also snatch Marche and Puglia from the left.
But all eyes will be on Tuscany, a historic left-wing stronghold that might fall to Matteo Salvini's far-right League.
“If the left performs particularly poorly… Brussels will grow concerned,” Berenberg economist Florian Hense told AFP.
It will worry whether the national recovery plan Italy has to present to obtain grants or loans to aid its ailing economy after the coronavirus lockdown “will be ambitious enough, given the limited political capital of the coalition in Rome,” he said.
“And whether, whatever plan Italy comes up with, it will actually implement it given the uncertain future of the current coalition”.
Concern over virus
The poll is going ahead despite warnings against opening polling stations while Covid-19 case numbers are on the rise.
While Italy currently has fewer new cases than Britain, France or Spain, it is still recording more than 1,500 daily.
“The country is in a state of emergency; it is utterly contradictory to be massing people together at polling stations, particularly in light of the trend in Europe,” Professor Massimo Galli, infectious diseases chief at Milan's Sacco hospital, told AFP.
He said previously that holding the elections now would be “madness”. Some precautions have been taken however, with elderly and pregnant voters getting fast-track lanes to vote.
With older people potentially put off voting by the health risks, the left has been organising special transport.
One in three of voters for the PD and League are over 65-years old, according to Italy's Corriere della Sera daily.
Nearly 2,000 voters in isolation due to the coronavirus have also registered to have their votes collected, including former prime minister Silvio Berlusconi.
But fear of catching the virus from voters obliged to pull down their masks to allow them to be identified has seen a flurry of last-minute desertions by polling station volunteers.
Milan was forced Saturday to call urgently for 100 fresh pairs of hands.
Prime Minister Conte has clinched a behind-doors deal with PD leader Nicola Zingaretti to fight to save each other's political skins should the left should perform disastrously, according to the Repubblica daily.
That might not be enough.
“These elections are not going to topple the government,” Political commentator Barbara Fiammeri for Italy's Sole 24 Ore daily told AFP.
“But there could well be a crisis, whether it be Conte's fall, the forming of new coalition, or even a national unity government”.