Manuel Pellegrini's side have a mountain to climb in the European contest, having suffered a 4-1 defeat when the two teams locked horns at Old Trafford last week.
Felipe has been an important player for the Green and Whites during the 2022-23 campaign, representing the club on 21 occasions in all competitions, including five outings in the Europa League.
The 25-year-old played the full 90 minutes of the game with Man United last week, but he was not involved against Villarreal on Sunday due to a hamstring problem.
Felipe's position in the selection has been taken by youngster Felix Garreta, but it is otherwise the same squad that was available against the Red Devils for the first leg.
William Carvalho will be available, returning to the squad after missing out against Villarreal through suspension.
Luiz Henrique will be suspended against Mallorca at the weekend due to the booking that he picked up against the Yellow Submarine.
However, the 22-year-old is available to feature against the 20-time English champions on Thursday night.
Nabil Fekir is out for the remainder of the campaign due to a serious knee injury, while Juan Cruz remains on the sidelines for Real Betis due to a hamstring issue.
Ayoze Perez, who is on loan at the club from Leicester City, scored for Pellegrini's side at Old Trafford last week, levelling the scores after Marcus Rashford had made the breakthrough.
However, Man United went on to score three more times through Antony, Bruno Fernandes and Wout Weghorst to secure a comfortable first-leg advantage.
Head coach Pellegrini has decisions to make when it comes to his starting XI for this match, with Sergio Canales and Borja Iglesias both pushing to be named in the side after only featuring as second-half substitutes in the first leg last week.
Willian Jose is also an option in the final third of the field, with the Brazilian finding the back of the net on two occasions in the Europa League this season.
Real Betis squad vs. Man United:
Bravo, Silva, Martin; Sabaly, Ruiz, Pezzella, Abner, Miranda, Felix; Edgar, Rodriguez, Canales, Henrique, Carvalho, Joaquin, Guardado, Rodri, Perez; Juanmi, Iglesias, Jose, Perez, Ruibal