On Thursday, student protesters marched through the city; the words "No Expo" were spray painted onto shop fronts, while policemen in riot gear patrolled the streets.
More demonstrations are expected on opening day, with a group known as NoExpo planning a procession through central Milan to coincide with May Day labor marches.
"We are expecting tens of thousands of people," Valentina Gazzara, a member of Off Topic, a group involved in the NoExpo movement, told CNBC via email.
"Expo is the event that promised jobs and wealth, but in fact led to the exploitation of voluntary labor, with an excessive load on overtime," she said, adding that many in Milan were unhappy about the event.
The NoExpo website also cited concerns over the involvement of multinationals like Coca Cola, McDonald's and Nestle.
But Piccoli said that he didn't think the protests would be particularly large or violent. He added that Italians are already disenchanted with the Expo, and that the launch event would not gain much traction at home.
"These people are already done with Expo. It's been attracting negative headlines for months because of delays and corruption allegations," he told CNBC. "It's even doubtful that Italian press will pay that much attention to the Expo. It's been a poorly handled opportunity."
The Expo press office did not respond to interview requests from CNBC.