The reverse fixture at Stadion Salzburg last week ended 1-0 in favour of the Austrian champions, leaving Jose Mourinho's team requiring a top performance on their turf to turn the tie around.
Match preview
This campaign has intermittently been frustrating for the Giallorossi in front of goal, and it was a familiar pattern in Austria last Thursday.
Mourinho's side hit the woodwork twice, missed a succession of big chances and were stunned by a well-directed Nicolas Capaldo 88th-minute header.
While no side in the competition has fashioned more promising opportunities than the Italians, no team in Europe's secondary club competition has missed more high-quality chances than the Rome outfit.
For a side trailing Salzburg heading into Thursday's meeting at the Olimpico, they need the requisite ruthlessness to avoid exiting the Europa League early.
They can draw inspiration from their goalscoring on home soil in the tournament, finding the back of the net seven times in the group stage. That tally is outdone by only four sides in the competition, giving supporters of the club hope of a comeback.
Be that as it may, Mourinho's team must avoid repeating mistakes from their only home loss in the competition, a 2-1 defeat by Real Betis, despite creating the game's best chances.
Matthias Jaissle's troops will back themselves against a team that has failed to find the back of the net or not score more than one goal in seven of their 11 games in 2023, including last week's inability to beat Philipp Kohn.
The Austrian giants were perhaps unfortunate to be drawn into the same group as Chelsea and AC Milan in the Champions League, where they ultimately ended third behind the pair despite going unbeaten in the opening four games of the group.
They may have fallen short of making the round of 16 in Europe's top club competition for the second season on the trot but find themselves halfway through reaching the Europa League's last 16 if they get the better of the Giallorossi in Rome.
Jaissle's free-scoring troops have netted in all but two competitive games in 2022-23, and that tendency to score stands them in good stead against a team that intermittently struggles to convert their openings.
With the jeopardy of away goals now lessened, Salzburg may need to beat Rui Patricio more than once at the Olimpico to advance.
Roma Europa League form:
W
L
D
W
W
L
Roma form (all competitions):
L
L
W
D
L
W
Red Bull Salzburg Europa League form:
W
Red Bull Salzburg form (all competitions):
L
L
L
D
W
W
Team News
Mourinho's squad is stretched thin, especially in attack, where they face a forward crisis.
Tammy Abraham suffered an eye injury in Sunday's 1-0 win over Hellas Verona and is likely to miss Thursday's game, Paolo Dybala did not feature, having gone off injured at half-time against Salzburg last week, and Lorenzo Pellegrini left group training on Monday due to a slight issue.
Nemanja Matic was rested against Verona, but the midfielder ought to return to play alongside Bryan Cristante in the middle of the park.
Jaissle made a few changes to his lineup in Salzburg's 3-1 Bundesliga victory over WSG Tirol, but there is an expectation to retain most of the starters from last week's win in Rome.
Amar Dedic and Oumar Solet should return in defence, while Noah Okafor and Fernando should return up top to play in tandem.
Maurits Kjaergaard was an unused substitute in the win over Roma last week but was the Red Bulls' best player in Sunday's league win and could tempt his manager to be selected from the off.
Roma possible starting lineup:
Patricio; Mancini, Smalling, Ibanez; Zalewski, Cristante, Matic, Spinazzola; Pellegrini, El Shaarawy, Belotti
Red Bull Salzburg possible starting lineup:
Kohn; Dedic, Solet, Pavlovic, Ulmer; Capaldo, Gourna-Douath, Seiwald; Sucic; Okafor, Fernando
We say: Roma 0-1 Red Bull Salzburg
Mourinho's men will most likely have to make do without Abraham and Dybala, leaving them short of the much-needed firepower up top in a game where goals are required to advance.
That should be music to the ears of the visiting Austrian side, who seldom fail to find the back of the net, a run that should continue in Rome.