The teams convene at Stadio Alberto Picco, after the hosts finished 16th and their visitors two places higher in May's final standings.
Match preview
Becoming part of the furniture in the Italian top flight, Spezia secured a third straight season in Serie A by a six-point margin last term, and now seek to challenge for a place in mid-table.
Since their long-awaited debut among Calcio's elite back in 2020, the Aquilotti have seen current Fiorentina coach Vincenzo Italiano and his successor Thiago Motta both keep them afloat, and now the baton is passed to Luca Gotti, who left Udinese midway through last season.
The former Chelsea assistant arrived in Liguria with something of a rebuild on his hands, as first-choice goalkeeper Ivan Provedel has left for Lazio, while centre-forward Rey Manaj strode through the exit door after his loan deal from Barcelona came to an end.
Nonetheless, veteran midfielder Albin Ekdal - once captain of Sampdoria - and Mattia Caldara (on loan from Milan) add experience to the squad, while Fiorentina outcast Bartlomiej Dragowski replaces Provedel.
Spezia's competitive bow for 2022-23 certainly went to plan for Gotti, as they crushed Como 5-1 in the first round of the Coppa Italia last weekend, with another loan signing, Daniel Maldini, scoring the final goal.
They now get their league campaign under way against opponents they held to a pair of draws last season, and will want to end their record of failing to win a Serie A opener at their third attempt.
Incidentally, Empoli are the team starting most Serie A seasons - currently 14 - without ever drawing their first match, and a record of 10 defeats during that time provides evidence as to their fortunes on opening night.
The Tuscans have also lost on six of the eight occasions they started a top-flight campaign away from home, but will hope to get off to a better start on Sunday, following a season of two halves in 2021-22.
With an early win over Juventus inflating the promoted side's confidence, Empoli surged into the top half of the table near the midway point, thanks to a fluent style under the experienced Aurelio Andreazzoli. However, a painfully long winless run was to follow; indeed no team won fewer games after the turn of the year - only two, alongside relegated Venezia.
Once safety had been belatedly assured, Andreazzoli was shown the door and Paolo Zanetti - Venezia's coach until the final weeks of the season - has since stepped in.
After positive signs in pre-season, which finished with four straight wins, a late Coppa Italia loss to Serie B side SPAL casts a shadow over the trip to Liguria, where new signing Mattia Destro could feature following the departure of last term's top scorer Andrea Pinamonti, who has signed for Sassuolo.
Spezia form (all competitions):
Empoli form (all competitions):
Team News
Already, Luca Gotti has a selection problem to unpick, as captain Giulio Maggiore has refused to play after being replaced as skipper by vice-captain Emmanuel Gyasi, having declined to sign a new contract at his local club.
Gyasi is likely to start up front for Spezia, in a forward line also featuring Daniele Verde, who has scored the most goals (14) for the Aquilotti in Serie A since promotion two years ago. In 2021-22 he was involved in 14 altogether (eight goals and six assists).
Gotti will be without the services of Janis Antiste, Kelvin Amian, Salva Ferrer and Albin Ekdal on Sunday, but new recruits Bartlomiej Dragowski and Mattia Caldara are set to start.
Meanwhile, Empoli have retained goalkeeper Guglielmo Vicario, who signed on a permanent deal following Cagliari's relegation, and he should join former teammate Razvan Marin in the visitors' starting XI - the latter replacing Kristjan Asllani, who has headed to Inter on loan.
Scottish midfielder Liam Henderson started in support of the front two in the Azzurri's Coppa Italia defeat last week, and he could do so again: playing behind Mattia Destro, who now represents his sixth Serie A club.
Lorenzo Tonelli remains out of action due to injury, but Paolo Zanetti otherwise has a clean bill of health within his squad before they head to La Spezia.
Spezia possible starting lineup:
Dragowski; Caldara, Kiwior, Nikolaou; Gyasi, Sala, Bourabia, Agudelo, Reca; Verde, Nzola
Empoli possible starting lineup:
Vicario; Stojanovic, Luperto, Ismajli, Parisi; Marin, Bandinelli, Haas; Henderson, Bajrami; Destro