A classic cup upset saw Vincenzo Italiano's inspired team knock out the nine-man Giallorossi on Tuesday and they now return to the scene of one of the great results in their history.
After a miserable week, when they were thumped by bitter rivals Lazio in the Derby della Capitale and then slumped out of the Coppa Italia to this weekend's unfancied opponents, Paulo Fonseca's Roma will be keen to restore some equilibrium to a previously positive campaign.
One of two competitions - along with the Europa League - for which they were realistic contenders this year, the 4-2 defeat will come as a heavy blow to Roma's morale.
Incredibly, another episode of administrative incompetence ensured that the Giallorossi would have been thrown out of the Coppa by default in any case, as they made six substitutions when only five were allowed - when the scoreline was still 2-2.
Earlier this season, they were penalised by a 3-0 defeat awarded versus Hellas Verona for fielding midfielder Amadou Diawara when he was ineligible to play.
Nonetheless, Fonseca's men now return to action still healthily placed in the Serie A standings - in fourth, on equal terms with Napoli - and with a record of three wins and a draw from their past four home games.
Thanks partly to Roma's self-inflicted implosion, Spezia managed to book a place in the Coppa Italia quarter-finals against Napoli - another high point in what is turning out to be a purple patch for the modest club.
Against the odds, in their only previous meeting, the lower-league Aquilotti had also emerged victorious at the Olimpico in 2015-16 - after a goalless draw was followed by victory in a dramatic penalty shootout.
This week's triumph was achieved as an increasingly established and respected Serie A outfit - one which sits 13th in the table and can reasonably aim to avoid a relegation battle in their first-ever season in the top flight.
Debutant Riccardo Saponara, on loan from Fiorentina, scored twice on Tuesday - once with an exquisite lobbed finish - and later hailed the "special" achievement of his new team. The experienced attacking midfielder could prove an inspired signing for coach Vincenzo Italiano during the second half of the Serie A season.
Having since enjoyed a private meeting with Pope Francis at the Vatican - receiving the football-loving pontiff's congratulations for their cup success - Spezia now look to continue a league run of two wins and a draw from their last three outings, which featured unexpected victories over both Napoli and Sampdoria.
At the moment, Italiano's men are being richly rewarded for their progressive approach to life at the elite level. However, Roma will be set on instant revenge at the Olimpico and are sure to come out all guns blazing.
Roma Serie A form: LWWWDL
Roma form (all competitions): WWWDLL
Spezia Serie A form: LLLWWD
Spezia form (all competitions): LLWWDW
Roma's Gianluca Mancini - also sent off in midweek - must serve a Serie A suspension, so will most likely be replaced by Chris Smalling in Paulo Fonseca's back three.
Still absent through injury, goalkeeper Antonio Mirante is covered by Mancini's fellow red-card villain, the hapless Pau Lopez. Meanwhile, first-choices Edin Dzeko, Jordan Veretout and Rick Karsdorp are expected to return to the XI after being rested in the cup.
Sent off early on in the brave 0-0 draw with Torino, Luca Vignali remains suspended for visitors Spezia, with defensive trio Elio Capradossi, Salva Ferrer and Federico Mattiello all doubtful due to injury.
Midfielder Matteo Ricci returned to the squad in midweek, after overcoming COVID-19, and should now regain his place in the Bianconeri's engine room. Top scorer M'Bala Nzola remains a concern for Vincenzo Italiano though, so Andrey Galabinov is favoured to keep his place up front in the French forward's probable absence - with young Roberto Piccoli another alternative.
Architect of their Coppa Italia victory, Riccardo Saponara should have done enough to earn a first league start for his new side, with Emmanuel Gyasi's place in jeopardy.
Roma possible starting lineup:
Lopez; Ibanez, Smalling, Kumbulla; Karsdorp, Veretout, Villar, Spinazzola; Pellegrini, Mkhitaryan; Dzeko
Spezia possible starting lineup:
Provedel; Erlic, Terzi, Chabot, Marchizza; Estevez, Ricci, Pobega; Saponara, Galabinov, Farias
We say: Roma 2-1 Spezia
Being stung twice in succession has glaringly highlighted Roma's defensive flaws - an issue which has dogged Paulo Fonseca since taking charge.
However, his talented side can bounce back - motivated by their embarrassment - and edge past a spirited Spezia outfit on Saturday.