Fabio Maresca will officiate the midweek Serie A game between Lazio and Atalanta, while Francesco Fourneau takes Benevento-Inter.
These are the rescheduled Week 1 fixtures, which were postponed because Atalanta, Inter and Spezia needed extra time to start their 2020-21 campaigns.
They all ended the 2019-20 season only a few weeks ago due to European or Serie B promotion play-off commitments.
Lazio-Atalanta will be officiated by Maresca, with Gianpaolo Calvarese in the VAR booth for this potential Scudetto showdown.
Benevento-Inter goes to Fourneau, with Luigi Nasca as his VAR.
Udinese-Spezia has Alessandro Prontera as the referee, with Luca Pairetto in the VAR seat.
They all kick off on Wednesday September 30.