The teams convene for a second-round Coppa Italia contest, with the Salentini having won just one league game this season and their visitors already on course for a quick return to the top flight.
Match preview
Lecce were on course for their second win in three games when Danish winger Patrick Dorgu put them a goal up against Parma last time out, and even after full-back Frederic Guilbert was sent off early in the second half they kept their noses in front.
Once their visitors were also reduced to 10 men, the Salentini even extended that lead through star striker Nikola Krstovic; however, conceding two stoppage-time strikes turned the game on its head as promoted Parma somehow salvaged a draw.
It was a bitter blow for Lecce boss Luca Gotti, whose team had admirably recovered from back-to-back losses to start the season, but now he must quickly turn his attention to the cup.
Gotti's side also scored twice in last month's season-opening Coppa Italia win over Mantova - with Krstovic netting a late winner on that occasion - which set up an intriguing second-round tie.
Before meeting AC Milan at San Siro on Friday evening, Lecce will meet opponents they took four points from in Serie A last season but have yet to beat in a top-flight match at Via del Mare.
Sassuolo's otherwise successful stay in the Italian top flight was brought to an untimely end last term, as the Emilian side failed to address a leaky defence and wound up slipping through the relegation trapdoor.
To spearhead their attempt to bounce back at the first attempt, former Lyon coach and 2006 World Cup winner Fabio Grosso was hired, with most of the Neroverdi's main men being persuaded to stay at the club.
Injured star Domenico Berardi is still on the books in Reggio Emilia, and French winger Armand Lauriente was on target in Saturday's 1-0 away win over Cosenza.
As a result of that three-point haul, Sassuolo occupy an automatic promotion place in Serie B, having lost just one game so far this season.
Grosso's side are still unbeaten on the road before heading south to Salento, for a tie booked by Lauriente's winner against Cittadella in the first round of this season's Coppa Italia.
Lecce Coppa Italia form:
W
Lecce form (all competitions):
W
L
L
W
D
D
Sassuolo Coppa Italia form:
W
Sassuolo form (all competitions):
D
W
D
L
W
W
Team News
Lecce boss Luca Gotti is sure to make several changes for his team's midweek cup clash, as there will be only three days to recover before they take on Milan.
Fringe players such as Kevin Bonifazi and Filip Marchwinski will feature in a long queue of hopefuls for promotion from the bench, while main marksman Nikola Krstovic may even be rested.
The hosts are set to be without Mohamed Kaba and Medon Berisha due to injury, but Lameck Banda made an appearance from the bench on Saturday and could now be ready to start.
Meanwhile, Sassuolo are still missing long-serving talisman Domenico Berardi, plus Matteo Lovato, who picked up an injury at the weekend; ex-Roma forward Cristian Volpato is struggling for fitness.
Former Venezia striker Nicholas Pierini could be in line for a return to the starting XI, having recently joined Armand Lauriente and Samuele Mulattieri among Fabio Grosso's attacking options.
Lecce possible starting lineup:
Fruchtl; Guilbert, Bonifazi, Jean, Pelmard; Ramadani, Pierret; Morente, Marchwinski, Banda; Rebic
Sassuolo possible starting lineup:
Satalino; Toljan, Odenthal, Romagna, Doig; Boloca, Obiang, Thorstvedt; D'Andrea, Mulattieri, Lauriente
We say: Lecce 1-2 Sassuolo
Sassuolo could compound Lecce's weekend woes, as the Serie B side look strong contenders for promotion this season and have some impressive attacking options.