The teams convene in Reggio Emilia with a last-16 tie against Atalanta up for grabs, and both will hope to start November successfully following a fruitless October.
Match preview
While their most recent wins came back-to-back, over Calcio giants Juventus and Inter, a tally of only two points from four fixtures since has seen Sassuolo slide down the Serie A standings and occupy a spot in the bottom half.
Having drawn with Lecce between home defeats to Monza and Lazio, the Neroverdi went into an Emilian derby against Bologna at the weekend with confidence diminished, and they fell behind following Joshua Zirkzee's superb first touch and finish as early as the third minute.
Daniel Boloca struck back just before the break, though, and Sassuolo ultimately settled for a 1-1 draw that sees them sit 15th in the table after 10 rounds of action.
Head coach Alessio Dionisi will be aware that his team's defensive deficiencies cannot continue if they are to challenge for a top-half finish this term, and they have now conceded at least one goal in each of their last 18 league matches.
Ahead of their trip to Torino on Monday, they return to a Coppa Italia campaign that started in August with a dramatic 5-2 defeat of Cosenza: after the Neroverdi conceded a last-minute goal, they then scored three times past 10-man opponents in extra time.
Like Sassuolo, as provincial outsiders, Spezia have never before lifted Italy's national cup, but more than a deep run in the Coppa their main aim for this season is bouncing straight back into Serie A at the first attempt.
Relegated after a tense playoff against Hellas Verona at the end of a tough 2022-23 campaign, the Aquilotti are yet to adapt to their surroundings in the second tier - with just one win to their name after 10 games, they are closer to the drop zone than the playoff places.
Three successive draws in October - two without scoring - leave Massimiliano Alvini's men with plenty of work to do in Serie B: having recorded only eight goals in the league, Spezia are ruing the departures of M'Bala Nzola and former captain Emmanuel Gyasi, both of whom secured summer moves to stay in the top flight.
The Ligurian club will meet fellow relegated side Cremonese - Alvini's former employers - at the weekend, but first the prospect of cup football can perhaps release some pressure on an underperforming outfit.
After losing 5-2 to Atalanta in the Coppa earlier this year, Spezia can meet the Bergamo side in the last 16 again this season by winning at the Mapei Stadium, where they lost 1-0 en route to demotion back in March.
Sassuolo Coppa Italia form:
W
Sassuolo form (all competitions):
W
W
L
D
L
D
Spezia Coppa Italia form:
W
Spezia form (all competitions):
L
D
W
D
D
D
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Team News
With one eye on an important game against Torino, Sassuolo coach Alessio Dionisi will make some changes to his side in midweek: injury-prone Domenico Berardi - who scored the spot-kick winner when these teams met earlier this year - is among those set to be rested.
Starts could therefore be handed to fringe players such as Samuele Mulattieri, back-up goalkeeper Alessio Cragno and Roma loanee Cristian Volpato.
Dionisi will again be without Matheus Henrique (hamstring), Pedro Obiang (thigh) and Agustin Alvarez (ACL), but Mattia Viti was back on the bench last weekend following his layoff with an adductor problem.
Meanwhile, Spezia's main fitness issue regards ex-Sassuolo midfielder Filippo Bandinelli, who has trained separately with a shoulder injury that forced him off in Saturday's Serie B draw with Cosenza.
More positively, Daniele Verde and German centre-back Lukas Muhl are close to returning and both may be available to feature at some stage.
Currently on loan from Thursday's hosts, Luca Moro is one of only three players to have scored more than once for the Aquilotti this season, so will hope to start against his parent club.
Sassuolo possible starting lineup:
Cragno; Pedersen, Viti, Erlic, Vina; Boloca, Racic; Defrel, Volpato, Castillejo; Mulattieri
Spezia possible starting lineup:
Dragowski; Amian, Gelashvili, Serpe; Elia, Zurkowski, Esposito, Cassata, Reca; Antonucci, Moro