The Seagulls trail by four goals following last week's capitulation in the Italian capital, which leaves them likely to exit in the last 16.
Match preview
Trailing 2-0 by half time, due to goals from Roma's star strikers Paulo Dybala and Romelu Lukaku, Brighton found their serene supremacy of the Europa League group phase sorely lacking at Stadio Olimpico last Thursday night.
Gianluca Mancini added a third for the hosts, before Bryan Cristante's diving header left Roberto De Zerbi's men facing a four-goal deficit, and if they are to extend their first campaign in UEFA competition then a minor miracle is required.
Already the first English club to lose so heavily in the knockout rounds, Brighton must make more history in order to salvage the situation: no team has overturned a four-goal deficit from the first leg of a Europa League tie to progress.
Hopes of a place in the quarter-finals are therefore slim for the European debutants, who bounced back from their chastening three-game losing run on the road with a much-needed victory at the Amex on Sunday afternoon.
Hosting relegation-threatened Nottingham Forest, Brighton ran out 1-0 winners, to reach 12 home games unbeaten in the Premier League and improve their prospects of another top-six finish this season.
The Seagulls are struggling to reach the same heights as last year, though, and De Zerbi will be keen to prove his team are not a spent force when close friend Daniele De Rossi visits England's south coast.
Having one foot in Friday's quarter-final draw, Roma continued to build momentum under new management at the weekend, when a last-gasp equaliser again showed their spirit at Stadio Franchi.
Diego Llorente's stoppage-time strike rescued a vital point for the Giallorossi in their fight for European qualification, and following a 2-2 draw with Fiorentina, they have lost just once in 11 games since De Rossi took charge, winning eight.
Only a 4-2 defeat at home to Serie A leaders Inter Milan has blotted his stellar record so far, but Roma's former midfield maestro will surely have to mend the capital club's Achilles' heel if they are to go all the way in Europe.
Europa Conference League winners in 2022, and Europa League finalists last year, the Eternal City side may have lost only one of their last 31 home matches in UEFA competition, but despite reaching successive finals under Jose Mourinho, they are winless in seven European knockout games on their travels.
Indeed, the history books suggest it could be a struggle to do the double over Brighton, as Roma have won just once in 22 previous trips to England - including 14 losses or draws since beating Liverpool in the 2000-01 UEFA Cup.
Brighton & Hove Albion Europa League form:
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W
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Brighton & Hove Albion form (all competitions):
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W
Roma Europa League form:
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Roma form (all competitions):
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Team News
As he seeks to orchestrate an improbable comeback, Brighton boss Roberto De Zerbi can call upon Scottish midfielder Billy Gilmour - who served the final match of his Premier League suspension at the weekend - but several players will still be missing on Thursday.
Solly March, Kaoru Mitoma and Jack Hinshelwood are all sidelined, alongside James Milner and Joao Pedro - the latter pair have thigh injuries - though Igor and Julio Enciso should both be fit enough to make the bench.
Without Joao Pedro - the Seagulls' six-goal top scorer in this season's Europa League - Danny Welbeck and Republic of Ireland striker Evan Ferguson are set to battle it out for selection up front.
With a healthy lead in the tie and one eye on Sunday's game against Sassuolo, Daniele De Rossi could be tempted to rotate his Roma squad, as fringe players such as Tommaso Baldanzi, Nicola Zalewski and Edoardo Bove come into his thinking.
Paulo Dybala has overcome his latest injury scare, while Rick Karsdorp returns from a knee problem, but Rasmus Kristensen and long-term absentee Tammy Abraham are still unavailable.
If not rested, Romelu Lukaku will try to set a new personal record for Europa League goals in a single season, requiring just one more to match his tally of eight for Everton in 2014-15. In all, Lukaku has now scored 27 times in UEFA's second-tier tournament and sits third on the all-time list.
Brighton & Hove Albion possible starting lineup:
Steele; Lamptey, Dunk, Van Hecke, Estupinan; Gilmour, Gross; Adingra, Lallana, Fati; Welbeck
Roma possible starting lineup:
Svilar; Celik, Mancini, Ndicka, Zalewski; Bove, Paredes, Pellegrini; Dybala, Lukaku, El Shaarawy