Starting Monday, Italians in the most populated regions will be required to stay home except for work, health or other essential reasons.
The whole country will be locked down on Easter weekend for the second year in a row from April 3-5.
Cases have been rising across the country in excess of 25,000 a day over the past six weeks, as Italy’s vaccination campaign is hit by delays.
Officials warn they are quickly losing ground in the fight against new, highly contagious variants.
Only 3 percent of the country is vaccinated, according to Johns Hopkins University data.
“Italy is administering about 170,000 doses a day — our aim is to triple that,” Prime Minister Mario Draghi said.
“It is only with widespread vaccinations that we will be able to do without restrictions like the ones we have had to adopt.”
More than 100,000 Italians have died from coronavirus complications, the second-highest toll in Europe after the UK.
Unlike last year, when Italy became the first western county to implement a nationwide lockdown, officials will allow for limited visits to friends and relatives over the Easter holiday.
Pope Francis’ Easter Vigil will likely be held earlier so that worshipers can abide by a 10 p.m. curfew.
Italians in non-essential jobs were also ordered to stay indoors over much of the Christmas and New Year’s holiday.
“I hope that this will be the last sacrifice asked of our citizens,” said Lombardy President Attilio Fontana.
Italian health officials Friday approved Johnson & Johnson’s single-dose vaccine. The doses will be delivered in a month, which leaders said will help efforts to fight back the surge.