The visitors, meanwhile, are hoping to end the campaign on a high and climb into the top half of the table.
Match preview
After winning four successive league matches by an aggregate score of 8-1, beating Juventus and Roma during this run, Lazio have since suffered back-to-back losses against Torino and Inter Milan.
A narrow 1-0 home defeat to Torino was followed by a 3-1 loss against Inter at San Siro last weekend, with goals in the final 13 minutes from Lautaro Martinez (2) and Robin Gosens turning the game on its head for the hosts after Felipe Anderson had given Lazio the lead on the half-hour mark.
Maurizio Sarri's side have never realistically been able to chase down Serie A champions-elect Napoli, and although Le Aquile remain second in the table, there is still work to be done in the final six games of the season to secure a place in next season's Champions League. Just four points separate Lazio from Inter, AC Milan and Roma in fourth, fifth and sixth respectively, while there is a six-point gap between Sarri's side and seventh-placed Atalanta BC.
With an intriguing fixture away against AC Milan coming up on Saturday, Lazio can ill-afford to drop any more points in Wednesday's clash with Sassuolo, against whom they have won their last two matches including a 2-1 home success last season.
Sarri's side also beat Sassuolo 2-0 on the road in January and another victory on Wednesday would see them complete their first Serie A double over the Neroverdi for five years.
Sassuolo managed to bounce back from a disappointing 3-0 defeat at Salernitana when they claimed a hard-fought 2-1 comeback victory at home against Empoli last weekend.
The Neroverdi's chances of securing maximum points looked bleak heading into the final 15 minutes as they were trailing 1-0 with 10 men after Andrea Pinamonti was shown a straight red card for dissent towards the referee following a tussle with Sebastian Walukiewicz.
However, substitute Domenic Berardi scored twice, including a dramatic 97th-minute penalty, to turn the game on its head and help Sassuolo move onto 43 points and climb to 12th in the Serie A standings.
With six games remaining, Alessio Dionisi's side still have a chance of bettering last season's 11th-placed finish and points total of 50, while a victory on Wednesday against Lazio would mathematically secure their place in the Italian top flight for next season.
Sassuolo have only won three of their eight Serie A away games since the turn of the year, but one of those was at the Stadio Olimpico against Lazio's city rivals Roma last month, coming out on top in a 4-3 thriller, and the Neroverdi will fancy their chances of beating an out-of-sorts Lazio outfit on Wednesday.
Lazio Serie A form:
W
W
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L
L
Sassuolo Serie A form:
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D
L
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L
W
Team News
Lazio currently have a clean bill of health, with left-back Luca Pellegrini recovering from a minor injury issue to make an appearance off the substitutes' bench against Inter.
Sarri is unlikely to make too many changes, if any, to his starting lineup, with a back four of Adam Marusic, Nicolo Casale, Alessio Romagnoli and Elseid Hysaj set to remain intact, protecting goalkeeper Ivan Provedel.
In-demand midfielder Sergej Milinkovic-Savic is expected to be joined in the middle of the pitch by Danilo Cataldi and Luis Alberto, while Anderson and Mattia Zaccagni - who both scored in the 2-0 away win at Sassuolo in January - are set to operate on the flanks either side of central striker Ciro Immobile.
As for Sassuolo, full-back Mert Muldur remains sidelined with a muscle injury, while striker Pinamonti is suspended following his dismissal last weekend.
Berardi recovered from a muscle problem to score a brace as a substitute last time out and the winger will be hoping to force his way back into the first XI at the expense of Nedim Bajrami.
Gregoire Defrel has scored only two goals in 21 Serie A appearances this season, albeit against AC Milan and Juventus, but he is expected to continue as the central striker in the absence of Pinamonti.
Lazio possible starting lineup:
Provedel; Marusic, Casale, Romagnoli, Hysaj; Milinkovic-Savic, Cataldi, Alberto; Anderson, Immobile, Zaccagni
Sassuolo possible starting lineup:
Consigli; Toljan, Erlic, Tressoldi, Marchizza; Frattesi, Lopez, Harroui; Berardi, Defrel, Lauriente
We say: Lazio 2-1 Sassuolo
Lazio have won six of their last 10 home league meetings with Sassuolo and they will be the favourites to come out on top on Wednesday despite their recent blip in form.
While an upset cannot be ruled out at the Stadio Olimpico, the visitors have lacked consistency in recent weeks and we believe that the hosts will edge a closely-fought contest.