Carlo Ancelotti's side host 17th-placed Real Valladolid and will be in confident mood following their emphatic 5-0 win at Almeria last Saturday.
The Catalans, six points clear of third-placed Los Blancos at the top of the table, face a daunting trip to Athletic Bilbao, who are unbeaten at their new stadium San Mames Barria.
Cristiano Ronaldo is set to start against Juan Ignacio Martinez's side, who will decend on the Santiago Bernabeu Stadium to challenge the Los Blancos surge to the top of the La Liga.
Ronaldo sat out the Champions League tie with Galatasaray in midweek but even without the man who has scored 25 goals in all competitions so far this season, Madrid won 4-1 to secure top spot in their group, despite having Sergio Ramos sent off after 26 minutes.
Speaking to the press before the Galatasaray game, Ancelotti insisted Ronaldo was "very confident" he would be able to recover in time to face Valladolid, although the coach made it clear he would not take any chances with the player's fitness.
Luka Modric, who was suspended in midweek and rested at Almeria, could also return to the side, but faces a challenge in ousting Isco from the team.
The former Malaga midfielder has been given a new lease of life since Sami Khedira was ruled out for the season with knee ligament damage, scoring twice in the last two matches and reproducing the performances which endeared him to the Bernabeu crowd at the start of the season.
One player who will definitely miss out is Alvaro Arbeloa, suspended after picking up five yellow cards this season. Dani Carvajal is set to deputise for the former Liverpool full-back.
Valladolid head into the game in a contrasting position to their hosts, losing 1-0 at home to Osasuna last week to go level on points with the two teams in the final two relegation spots.
They will be without suspended winger Patrick Ebert and midfielder Oscar Gonzalez, who is carrying a knee problem.
Striker Javi Guerra acknowledged the disparity in quality between his side and Madrid, but declared Valladolid had not given up all hope of getting a result.
"Nothing is impossible in football and that's the mentality we'll take with us into the game," he told a press conference.
"We know it's going to be very difficult but at the end of the day this is football, it's 11 against 11 and although of course Real Madrid are a better team than us, they will have to prove that on the pitch."