While the Rome club top the table with a flawless record at the halfway stage, their Bulgarian counterparts have yet to win and sit 34th in the 36-team standings.
Match preview
Lazio have not reached the Europa League's knockout rounds in any of their last three appearances but are on track to do so this season, having steamed away from the start line in the new-look league phase.
The only team still with a 100% record in UEFA's second-tier competition, the Biancocelesti have won four from four so far, and they are now 90 minutes away from posting five consecutive victories in Europe for the very first time.
Last time out, Marco Baroni's men were 2-1 winners at home to Porto, as veteran forward Pedro continued his purple patch by scoring a last-gasp goal to snatch back maximum points after Alessio Romagnoli's opener had been levelled.
Previous successes against Twente, Nice and Dynamo Kyiv had already left Lazio in a strong position to claim one of eight automatic spots in the last 16, and they now have a five-point buffer to ninth place.
Such superb form has not been limited to continental competition, as the Aquile are also excelling in the Italian top flight: Sunday's 3-0 win over 10-man Bologna made it seven straight wins for the first time in seven years, and they sit just one point behind leaders Napoli at the Serie A summit.
Lazio have faced Ludogorets twice before, in a two-legged Europa League tie back in 2014, when the Bulgarian side progressed as aggregate winners after an eventful 3-3 draw at home.
The Eagles' 1-0 away victory in the first leg saw both teams miss a penalty and have a player sent off, and a repeat result would be warmly welcomed by the visitors this week.
After Ludogorets were beaten 2-1 at home by Athletic Bilbao earlier this month, they continue to languish in the elimination places, lying third from bottom of the table with just one point on the board.
Having kicked off their campaign with a 2-0 defeat against Slavia Prague, followed by a goalless draw with Viktoria Plzen, the Razgrad club conceded two second-half goals to suffer another loss against Anderlecht. As it stands, though, they are still only three points shy of a playoff place, with four games left to turn things around.
While head coach Igor Jovicevic is still awaiting his team's first win of the league phase, Ludogorets remain dominant in Bulgaria's First League: undefeated this season, they have won 13 of their 15 matches to establish a seven-point lead at the top of the table.
Only a stoppage-time equaliser saw them denied an away win over CSKA Sofia at the weekend, but their next road trip will be much more formidable.
Lazio Europa League form:
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Lazio form (all competitions):
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Ludogorets Razgrad Europa League form:
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Team News
As has been the case throughout the league phase so far, Marco Baroni is set to rotate his squad on Thursday evening, ahead of a busy few weeks that will see Lazio meet Napoli twice, then Ajax and Inter Milan.
After being substituted at half time against Bologna due to a calf issue, centre-back Alessio Romagnoli could be rested, while captain Mattia Zaccagni picked up a knock and may also sit out the Biancocelesti's midweek match. In-form left-back Nuno Tavares is definitely sidelined by a muscular injury.
A scorer in the 2019 final, 37-year-old Pedro has found the net in each of his last three Europa League appearances, and he can now become the oldest player to score four in a row, beating Spanish compatriot Aritz Aduriz (36 years, 299 days).
Meanwhile, Ludogorets will travel to the Eternal City without two of their Brazilian contingent, Rick and Caio Vidal, both of whom are suspended.
Bulgaria internationals Georgi Rusev and Ivalyo Chochev are therefore contenders to come into the team that were held to a 2-2 draw by CSKA Sofia on Sunday.
Midfielder Pedrinho is available after serving a one-match ban for an accumulation of yellow cards, and he could join Erick Marcus - scorer of the Eagles' only goal so far - in the starting XI.
Lazio possible starting lineup:
Mandas; Marusic, Gila, Gigot, Pellegrini; Vecino, Rovella; Tchaouna, Dele-Bashiru, Pedro; Dia
Ludogorets Razgrad possible starting lineup:
Padt; Fonn Witry, Verdon, Almeida, Son; Rusev, Duarte, Pedrinho, Chochev, Marcus; Duah
We say: Lazio 2-0 Ludogorets Razgrad
Not only are Lazio in scintillating form, having won 11 of their last 12 matches, their fellow 'Eagles' rarely fare well on the road.