Sassuolo, meanwhile, have already played their first league game, drawing 1-1 with Cagliari, and will hope to improve on that result as they build on last season's eighth-placed finish.
Spezia finished third in Serie B last season and won promotion via the playoffs, beating Chievo Verona and Frosinone.
In 2008, the club was forced to declare bankruptcy after being relegated from the second tier and was refounded, starting the 2008-09 season in Italy's fourth tier.
After 12 years, though, the club has finally clawed its way into the top flight and will hope to give a good account of themselves.
They take on Sassuolo, who themselves entered Serie A for the first time in their history in 2013 - and have remained there since - and Spezia will hope to follow in their opponent's footsteps.
Sassuolo finished eighth in Serie A last term - their highest top-flight finish since they placed sixth in the 2015/16 season - and will hope to kick on this time around.
Their stalemate at home against Cagliari, while disappointing, was perhaps to be expected, given the two sides drew both their league meetings last term.
In Spezia, though, Sassuolo will see an opportunity to pick up their first win of the campaign, with their newly-promoted opponents likely to require an adaptation period.
Sassuolo will also be hoping to avoid the stuttering start they endured last season, only winning two of their first seven league games.
Spezia Calcio Serie A form: N/A
Sassuolo Serie A form: D
Spezia head coach Vincenzo Italiano has a couple of players unlikely to be able to feature against Sassuolo through injury.
Meanwhile, Sassuolo boss Roberto De Zerbi has the same number of players out, but with more serious injuries.
Francesco Magnanelli is set to be sidelined until early November with a hernia.
Filippo Romagna's situation is far worse, however, with the defender ruled out for the season with a knee injury.
Spezia Calcio possible starting lineup:
Zoet; Ferrer, Erlic, Terzi, Ramos; Bartolomei, M. Ricci, Maggiore; F. Ricci, Galabinov, Gyasi
Sassuolo possible starting lineup:
Consigli; Toljan, Chiriches, Ferrari, Rogerio; Obiang, Locatelli; Berardi, Duricic, Haraslin; Caputo
We say: Spezia Calcio 0-2 Sassuolo
Sassuolo have proven themselves a good outfit recently and should have little trouble claiming all three points from Serie A debutants Spezia.