The hosts could climb to the summit of the group with a victory, while the visitors, who have already qualified for the knockout rounds, will secure top spot if they avoid defeat.
Match preview
Ludogorets have been somewhat of a surprise package in this year's Europa League group stage and they still have a strong chance of progressing to the knockout rounds for the first time in three seasons.
The Eagles accumulated just two points and failed to win any of their six group games last season, but they have already picked up seven points after four matches so far this term, including a memorable 2-1 home triumph against Roma in matchday one.
Ante Simundza's side secured a 2-0 victory at home against HJK Helsinki in their most recent Group C fixture, courtesy of strikes from Denny Gropper and Rick, and they have moved to within three points of Thursday's opponents Real Betis at the top.
Ludogorets head into their latest Europa League clash in good form having won each of their last four matches in all competitions, including their last two Bulgarian First League games against Beroe and Botev Plovdiv by an aggregate score of 5-0.
However, extending their winning streak could prove challenging as they have lost all seven of their previous meetings with Spanish opposition, including a 3-2 away loss to Real Betis in matchday two.
Real Betis saw their seven-game unbeaten home run come to an end last weekend as they suffered a 2-1 La Liga defeat against Atletico Madrid.
Antoine Griezmann netted a brace to put the visitors two goals in front, and although substitute Nabil Fekir on his return from injury pulled one back for the hosts, Manuel Pellegrini and co were condemned to just their third defeat of the campaign.
Los Verdiblancos have won only one of their last five games across all tournaments, but they are one of only six teams in this season's Europa League who remain unbeaten after four group matches, winning three times and drawing once.
Indeed, their perfect record in Group C came to an end last time out as they played out a 1-1 draw at home against Roma, with Sergio Canales's opener cancelled out by Andrea Belotti.
Nevertheless, Betis will advance to the knockout rounds as group winners for the first time in four years if they avoid defeat in Bulgaria on Thursday, while securing maximum points would see them claim three successive away wins in European competition for the very first time.
Ludogorets Razgrad Europa League form:
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Real Betis Europa League form:
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Team News
Ludogorets duo Kiril Despodov and Dominik Yankov are both set to miss out with respective thigh and knee injuries, while Claude Goncalves is doubtful with a back problem.
Simundza is expected to name the same side that beat HJK two weeks ago, with Bernard Tekpetey, Cauly and Rick providing support in attack for central striker Matias Tissera.
After scoring in the 1-0 league win over Botev Plovdiv last weekend, Jakub Piotrowski could keep his place in centre-midfield alongside either Manuel Cafumana or Nonato.
As for Real Betis, Spanish attacker Juanmi is ruled out until the beginning of January with an ankle injury, while midfielder Andres Guardado is suspended after receiving three yellow cards in the group stage.
Canales, who missed the defeat against Atletico due to suspension, and Fekir will both be pushing to start, and either playmaker could replace the suspended Guardado, with William Carvalho and Guido Rodriguez operating in deeper midfield roles.
Goalkeeper Claudio Bravo has started all four Europa League games between the sticks and he is expected to continue in the first XI on Thursday ahead of Rui Silva.
Ludogorets Razgrad possible starting lineup:
Padt; Cicinho, Verdon, Nedyalkov, Gropper; Piotrowski, Cafumana; Tekpetey, Cauly, Rick; Tissera
Real Betis possible starting lineup:
Bravo; Ruibal, Felipe, Pezzella, Miranda; Carvalho, Rodriguez; Rodri, Canales, Joaquin; Iglesias
We say: Ludogorets Razgrad 1-2 Real Betis
Ludogorets will fancy their chances on home soil having already beaten both Roma and HJK in front of their own fans, and they pushed Real Betis all the way in the reverse fixture despite losing 3-2 in Spain.