The Napoli right-back picked up his third booking of the preliminary period in last month's 3-1 loss to England, which left Italy three points behind Ukraine in third place in the section.
The Azzurri boast a game in hand and overcame Ukraine in their opening Group C encounter, though, so a draw will suffice against the Blue and Yellows on Monday if they can put North Macedonia to the sword.
However, they will have to do so without the banned Di Lorenzo, while all of Rafael Toloi, Alex Meret, Manuel Locatelli and Davide Calabria have pulled out of the squad with injuries.
None of Destiny Udogie, Gianluca Mancini, Ciro Immobile or Giorgio Scalvini are at Spalletti's disposal either, although Federico Dimarco is a straight swap for the former on the left-hand side of the backline.
Dimarco could potentially form an all-Inter Milan defence in front of Gianluigi Donnarumma, who should be shielded by the central pairing of Alessandro Bastoni and Francesco Acerbi, while Matteo Darmian ought to fend off Manuel Lazzari to deputise for Di Lorenzo.
The returning Jorginho is expected to be deployed as the deepest-lying midfielder - a role he has often occupied for Arsenal in recent weeks - most likely with another two Nerazzurri representatives in Davide Frattesi and Nicolo Barella alongside him in the engine room.
With Immobile missing again, Gianluca Scamacca should be given the nod up front following his goal against England last month, as Federico Chiesa and Domenico Berardi line up in support of the Atalanta BC man.
Italy possible starting lineup: Donnarumma; Darmian, Acerbi, Bastoni, Dimarco; Barella, Jorginho, Frattesi; Berardi, Scamacca, Chiesa