Carlo Ancelotti's men sit third in La Liga but can catch at least one of the top two with a win in Catalunya at the weekend.
With Barca and Atleti playing each other on Saturday, Carlo Ancelotti's side will make ground on one or both of them if it can take a win over Espanyol.
Espanyol has endured an inconsistent season under Javier Aguirre so far with only six league wins, although one of those did come against Atletico at El Prat in October.
The Mexican will not be on the sidelines after being sent to the stands during last week's 1-0 defeat to Osasuna and subsequently being found guilty of abusing the referee and given a four-match ban.
Stopping Real Madrid will be difficult given the 32-time league winner has amassed 31 goals in its last eight Liga matches, with forward Cristiano Ronaldo getting 12 of those to take him to the top of the goalscoring charts in Spain with 20 for the campaign.
The Portugal international is one of the most in-form players across the continent and is odds-on favourite to lift the Ballon d'Or on Monday after his displays in 2013.
Espanyol has earned draws in its last two meetings with the Blancos, however the club comes into the game on the back of consecutive defeats in La Liga and Wednesday's first-leg Copa del Rey tie with second-tier Alcorcon.
Raphael Varane and Sami Khedira (both knee) are the only players unavailable for the visiting side but Aguirre will be without his captain Sergio Garcia through suspension and David Lopez after he picked up a thigh injury in midweek.