Top-flight survival is on the agenda for the visitors though, as they enter the season finale level on points with Hellas Verona in a two-way battle to avoid the drop.
Match preview
After taking a first-half lead in Budapest in midweek, much of Europe expected Jose Mourinho to produce another frustrating masterclass to claim a second-consecutive continental crown for Roma.
However, Gianluca Mancini's own goal changed all that and Sevilla were always in the ascendancy from there on in, before the aforementioned Mancini and Roger Ibanez both missed from the spot in a resultant penalty shootout they went on to lose.
Mourinho had essentially given up on domestic matters to focus purely on Europe after Roma reached the semi-finals, and it has backfired spectacularly.
With all their rivals for the top four going through poor spells of their own, the Giallorossi could have easily finished in a Champions League spot, but not many sides have put together a worse run of results than them in the last two months across all of Europe.
The top-four picture is already decided after AC Milan's win at Juventus last Sunday, but Roma still need a win to ensure they make the Europa League, with Massimiliano Allegri's side breathing down their neck.
The seven games Roma have played in Serie A since progressing past the quarter-finals in Europe have yielded a remarkably low four points, in which they have won none.
With just 48 goals scored this campaign, this could be the first time since the 1950-51 season where Roma end a 20-team Serie A season having scored fewer than 50 goals, and that year they finished 19th.
Spezia are favourable opponents though, as Roma have never lost to them in Serie A, and boast a record of four wins in the last five encounters.
Home form has been relatively strong for Mourinho's side too, especially after scoring first, as they are unbeaten in the 11 home games where they have scored the opening goal this season.
That is a bad omen for Spezia, as they are the club who have scored the opening goal on the fewest occasions in Serie A during 2022-23.
Leonardo Semplici's men start the day outside the relegation zone, but curiously, safety is still out of their hands for this weekend at least.
Coming into effect from this season, if the two sides finishing 17th and 18th end on the same points, a relegation playout at a neutral venue will be played, regardless of the head-to-head record and goal difference.
Spezia and Verona start the weekend tied on 31 points, so should they match each other's result, then the playout will take place.
Therefore, even though they start the weekend outside the bottom three, if Verona win at Milan, Spezia cannot confirm safety here.
Prospects either way are not great for Spezia, given that they were thrashed 4-0 at home to a Torino side with nothing to play for last weekend.
In their 19 Serie A fixtures since mid-January, they have just two wins, losing 10 in the process.
Remarkably though, both wins came against the two Milan clubs, who were Champions League semi-finalists, and the Spezia faithful will be hopeful that Roma's exploits in Europe may be a distraction to them too.
Ironically, Spezia will be wishing for Milan to do them a favour, considering they are the side hosting Verona simultaneously to this fixture, but history suggests otherwise.
'Fatal Verona' is the nickname given to Hellas by Milan supporters after they were the club who cost the Rossoneri two titles by beating them late in the season in years gone by.
Roma Serie A form:
D
D
L
D
D
L
Roma form (all competitions):
W
D
D
D
L
L
Spezia Serie A form:
L
L
L
W
D
L
Team News
Mourinho's team selections have varied wildly in recent weeks as they have prioritised Europe, but he could return to something close to a strong XI here.
Stephan El Shaarawy did not start in Budapest, but he has scored three goals in his last three Serie A starts, taking his chance in the side with both hands.
One player who has not done so is Andrea Belotti, as the Euro 2020 winner is yet to score in 30 league games for Roma since arriving from Torino last summer.
Rick Karsdorp and Marash Kumbulla are the only known absentees, but a few more may drop out of the squad after Wednesday's heartache.
There will be no rotation for Spezia, as everything is on the line for them, and there are no new injury concerns from last weekend.
Emil Holm, Joao Moutinho and Petar Zovko have all been long-term absentees, and remain Spezia's only injury concerns.
M'Bala Nzola has won 16 points for Spezia with his 13 goals this season - more points than any other player in the division - so his influence will be absolutely critical if Spezia are to have a chance of survival.
Roma possible starting lineup:
Svilar; Mancini, Smalling, Ibanez; Zeki Celik, Wijnaldum, Cristante, Zalewski; El Shaarawy, Belotti, Pelligrini
Spezia possible starting lineup:
Dragowski; Wisniewski, Ampadu, Nikolaou; Amian, Ekdal, Esposito, Bourabia, Reca; Gyasi, Nzola
We say: Roma 2-1 Spezia
Despite Roma's heartache in midweek, Mourinho should be able to get his players motivated for one last push in what could be his late game in charge.