After a dramatic late win last time out, the Eagles are contending for a top-eight finish, while their Italian counterparts fell five points adrift of the playoff places following a defeat by Lille.
Match preview
Scoring twice in the final six minutes of an enthralling encounter with Monaco, Benfica snatched a 3-2 victory from the jaws of defeat last month, moving the Portuguese giants onto nine points in the league phase table.
Taking advantage of their hosts going down to 10 men, Bruno Lage's side turned things around thanks to late goals from Arthur Cabral and Zeki Amdouni, which followed an earlier strike from Vangelis Pavlidis - only three teams have had more different scorers in this season's Champions League.
Lage has also recorded eight wins from as many league matches since taking charge in September - following a 1-0 home win over Vitoria SC on Saturday - and his second spell at Estadio da Luz has started spectacularly.
Surging to within two points of city rivals Sporting CP in the Primeira Liga standings, Benfica have won all of their last 11 domestic fixtures and are unbeaten in 14 since the opening day of the season.
Having revived an inconsistent squad and found a winning formula, he is now intent on wrapping up at least a Champions League playoff place, which victory on Wednesday would effectively achieve - finishing in the top eight is still possible too.
However, Benfica have won just one of their last six home matches in Europe's top club competition, after following up a fine 4-0 win over Atletico Madrid on the second matchday with a 3-1 loss to Feyenoord.
While Benfica are seasoned campaigners in continental competition, Bologna are Champions League rookies, now facing their first game against Portuguese opponents since September 1998, when they beat Sporting 2-0 in the UEFA Cup.
The Rossoblu's league-phase debut began with a goalless draw at home to Shakhtar Donetsk, but they have been defeated four times since - and they had to wait until last month's 2-1 loss to Lille to score their first goal.
As well as being Bologna's sole scorer to date, Colombian defender Jhon Lucumi has also made the most interceptions, completed the most passes, made the most clearances and won the most aerial duels for his side, drawing interest from clubs higher up the food chain.
His attacking colleagues have come up short, though, and now in need of three wins from their final three games, Vincenzo Italiano's men must be more ruthless in front of goal.
The only team yet to find the net from open play - failing to convert any of 41 attempts on goal - Bologna have already suffered 2-0 defeats at Liverpool and Aston Villa, so they could become the eighth different club to lose their first three Champions League away games without scoring.
On the domestic scene, they have recently shown signs of improvement after a slow start to Italiano's reign, edging up to eighth place in Serie A and advancing to the Coppa Italia quarter-finals.
On Saturday, the Emilian side let a two-goal lead slip through their fingers in Turin, costing them a rare win over Juventus side managed by their former boss Thiago Motta, who was sent off before Juve produced a late fightback.
After Dan Ndoye and Tommaso Pobega scored to put Bologna in control, they ultimately conceded a 92nd-minute equaliser - consigning them to an eighth draw in 20 games this season.
Benfica Champions League form:
W
W
L
L
W
Benfica form (all competitions):
L
W
W
W
W
W
Bologna Champions League form:
D
L
L
L
L
Bologna form (all competitions):
W
L
L
W
W
D
Team News
Benfica boss Bruno Lage can welcome playmaker Orkun Kokcu back from suspension in midweek, when he will have most of his squad available; only Renato Sanches will be missing due to a thigh injury that has kept the former Paris Saint-Germain midfielder sidelined since early November.
Sure to start in the final third, veteran forward Angel Di Maria registered his 37th and 38th assists in the Champions League last time out, taking him clear of David Beckham into fourth place on the all-time list.
The Argentinian has racked up six goals and three assists in his last five appearances across all competitions, while Kerem Akturkoglu is the Eagles' top scorer this season with 10 goals.
Meanwhile, Bologna's main threat Riccardo Orsolini limped out of their 4-0 Coppa Italia win over Monza last week and is now struggling to overcome a thigh strain.
Michel Aebischer and Charalampos Lykogiannis have recently been hit by muscular injuries, and both could join long-term absentees Nicolo Cambiaghi and Oussama El Azzouzi in missing the trip to Portugal.
The visitors' attack should be led by 20-year-old striker Santiago Castro, who has notched five goals and five assists across all competitions this season.
Benfica possible starting lineup:
Trubin; Bah, Araujo, Otamendi, Carreras; Aursnes, Luis, Kokcu; Di Maria, Pavlidis, Akturkoglu
Bologna possible starting lineup:
Skorupski; Posch, Beukema, Lucumi, Miranda; Freuler, Pobega; Ndoye, Ferguson, Dominguez; Castro
We say: Benfica 2-0 Bologna
Only one of Benfica's last 36 UEFA fixtures has finished goalless, and they are scoring freely at the moment - with plenty of attacking options available on the bench if Bruno Lage requires 'Plan B'.
Written by
Jonathan O'Shea