Azzurri debut for Polledri
The 22-year-old Glouchester flank replaces Maxime Mbanda who suffered a knee injury during Italy's 14-38 defeat to Wales in their fourth game in Cardiff last weekend.
Irishman O'Shea made just one change on the bench, with flank Braam Steyn replacing Federico Ruzza.
England-born Polledri will join Sebastian Negri and captain Sergio Parisse in the back row with Giulio Bisegni alongside Tommaso Castello in midfield.
The back three of Matteo Minozzi – who scored his third try of the tournament in Cardiff – Mattia Bellini and Tommaso Benvenuti also remains unchanged.
Alessandro Zanni – who earns a 50th Six Nations cap – and Dean Budd make up the second row with Leonardo Ghiraldini at hooker with Andrea Lovotti and Simone Ferrari props.
"This group has learned so much in this Six Nations," said O'Shea as Italy chase their first win in the competition since 2015 in Edinburgh.
"It's possible for us to beat anyone, if only we can control what we want in the important moments of the match.
"It's difficult because we want to win right away but I'm 100 percent sure we're on the right track.
"We have started a journey that will allow us to grow year after year, even after the World Cup."
He added: "We want to win against Scotland. We know that there are two or three key moments in a game, if we catch them, maybe we will win on Saturday."
Scotland are looking for their third victory this season after home wins over France and England.
The two sides have met 28 times with Scotland leading 20-8.
Italy are bottom of the table, without a Six Nations win since their visit to Murrayfield in 2015.
In the Six Nations, Scotland beat Italy 29-0 in Edinburgh last year and were 36-20 winners in Rome in 2016.
Italy: 15 Matteo Minozzi, 14 Tommaso Benvenuti, 13 Giulio Bisegni, 12 Tommaso Castello, 11 Mattia Bellini, 10 Tommaso Allan, 9 Marcello Violi, 8 Sergio Parisse, 7 Jake Polledri, 6 Sebastian Negri, 5 Dean Budd, 4 Alessandro Zanni, 3 Simone Ferrari, 2 Leonardo Ghiraldini, 1 Andrea Lovotti.
Replacements: 16 Oliviero Fabiani, 17 Nicola Quaglio, 18 Tiziani Pasquali, 19 Abraham Steyn, 20 Giovanni Licata, 21 Guglielmo Palazzani, 22 Carlo Canna, 23 Jayden Hayward.
Date: Saturday, March 17
Venue: Stadio Olimpico, Rome
Kick-off: 13.30 (12.30, 12.30 UK time)
Referee: Pascal Gaüzère (France)
Assistant referees: Jérôme Garcès (France), Andrew Brace (Ireland)
TMO: Marius Jonker (South Africa)
AFP
