Zinedine Zidane's side will end a disappointing campaign in third place, while Los Verdiblancos have seen their hopes of Europe fizzle out after a promising start.
Last term Quique Setien saw his side record a famous 1-0 win at the Bernabeu, and with mounting speculation about his future, the Betis boss will be hoping for another strong performance in what could be his last game in charge.
The hosts have won all five home matches they have played since Zidane returned as manager and bet365 offer them at 4/6 (1.66).
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Sergio Ramos has been missing for the last month but should return on Sunday. Gareth Bale is fit but has been left out of the last two matchday squads by Zidane and it remains to be seen if the Welshman will feature this weekend.
Betis are without midfielder Sergio Canales and full-back Antonio Barragan.
Real Madrid's lacklustre end to the season has seen them face motivated teams with much more to play for than Los Blancos themselves.
Betis, however, have nothing on the line, and two wins from their last nine games underlines just how underwhelming they have been in the last couple of months.
Only two sides have lost more games away from home than Betis this season, while their total of 17 goals scored on the road in 18 matches is the fourth-lowest total in the division.
Madrid should be able to see them off and continue their winning run at home, although it is likely to be something of a low-key affair.
Tips and predictions
The Bernabeu outfit have won 13 home games in La Liga, 10 of which have come with under 3.5 goals and a repeat is priced at an attractive looking 12/5 (3.40).
Betis have lost 10 away games this term, eight of which have come with under 3.5 goals, making this selection extremely appealing.
Odds correct at the time of writing. Please gamble responsibly.