The two neighbours have already met this year in the Copa Del Rey - with Leganes knocking out Zinedine Zidane's side - and Real Madrid will be keen to exact some revenge for that shock defeat.
Zidane's men are offered at 2/7 (1.28) with dabblebet to win at the Estadio Butarque where last month they triumphed by a 1-0 scoreline before losing at the Bernabeu.
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For Real Madrid, Toni Kroos and Marcelo are likely to be unavailable through injury.
Leganes should be boosted by the return of a number of key players, including top scorer Gabriel Pires and defenders Mauro Dos Santos and Tito.
Leganes' attacking woes to continue
Leganes have gone four matches in all competitions without scoring and their lack of a clinical edge has been their main problem all season in La Liga.
Los Pepineros' total of 10 home goals scored is the second lowest total in the Primera Division and six of their ten league games at the Estadio Butarque have seen under 1.5 goals.
Whilst Real Madrid have been scoring freely in recent weeks, Leganes have shown they can frustrate them and with Zidane likely to rotate his squad, it might be another low-scoring game.
Preview and predictions
This bet paid out when the sides met at Butarque in the Copa Del Rey last month and has proved profitable of seven of Leganes' ten home games this term.