Barcelona slipped to only their second defeat of the season, while Inter Milan remain in control in Italy.
Hamburg moved back to the Bundesliga summit and Lyon took advantage of slip-ups from their rivals to take another step closer towards an eighth consecutive title.
AZ Alkmaar continue to set the pace in Holland, while Rangers now lead the way in Scotland after a disappointing weekend for Celtic.
Barcelona had gone 22 games since they last tasted defeat heading into the weekend, but were shocked 2-1 by city rivals Espanyol.
Former Camp Nou favourite Ivan De La Pena came back to haunt his former employers as his brace secured local bragging rights in Catalunya.
That setback allowed Real Madrid to close the gap at the top to seven points as the capital club proved far too strong for Real Betis.
Heading into a crunch week of European action, two goals apiece from strike duo Raul and Klaas Jan Huntelaar helped Juande Ramos' men to a comprehensive 6-1 win at Santiago Bernabeu.
Seville are now third after a solitary strike from Jesus Navas saw them past Atletico Madrid, while Villarreal remain inside the UEFA Champions League places after a 2-1 success at home to Sporting Gijon.
Inter Milan are edging closer to a fourth league title in as many years after they maintained their nine-point advantage over the chasing pack.
Jose Mourinho's men were pushed all the way by lowly Bologna on Saturday, but were able to grind out a 2-1 win.
Juventus continue to provide the biggest challenge to Inter's dominance, with the Turin giants overcoming Palermo 2-0 this weekend in a game which saw David Trezeguet make a welcome goalscoring return to action.
AC Milan kept their faint hopes of title glory alive with a narrow 1-0 victory at home to Cagliari, with Clarence Seedorf helping to ease some of the mounting pressure on Carlo Ancelotti's shoulders.
Martin Jol's Hamburg lead the way in Germany after they saw off Bayer Leverkusen on Sunday.
The in-form Marcell Jansen was once again on target as he notched what proved to be the decisive goal in a 2-1 win.
Hoffenheim are now two points off the pace after they were held in a six-goal thriller with Stuttgart.
Hertha Berlin lost ground after they threw away a one-goal lead to lose 2-1 on the road at Wolfsburg.
Bayern Munich slumped to back-to-back defeats as they went down 2-1 at home to Cologne, while Claudio Pizarro was unceremoniously dumped from Werder Bremen's squad for their 2-1 defeat at Energie Cottbus.
A good weekend for Lyon saw Claude Puel's men stretch their lead at the summit to six points.
Karim Benzema was on the scoresheet for the reigning champions as they secured a 2-0 win at Nancy.
Paris St Germain remain in second spot but the capital club were held to a goalless draw on Saturday by Grenoble.
Marseille missed the opportunity to move above their arch rivals 24 hours later as they were held 0-0 by Le Mans.
AZ Alkmaar continued their procession towards claiming the Eredivisie crown on Saturday with a comfortable 2-0 win away at struggling Heracles.
Steve McClaren's FC Twente remain within nine points of the leaders after a hard-fought 2-1 victory over Sparta Rotterdam, but time is not on their side.
Ajax came from behind to take maximum points from their home date with Volendam, running out 2-1 winners.
Rangers are the new leaders in Scotland after they usurped Old Firm rivals Celtic at the summit.
Two goals from Kenny Miller and a 24th of the season from Kris Boyd eased Walter Smith's side to a 3-1 victory over Kilmarnock at Ibrox.
Celtic then missed the opportunity to reclaim top spot on Sunday as they were held 1-1 by Motherwell at Fir Park.
Best of the rest
Olympiakos suffered a rare defeat in Greece, going down 1-0 at Ergotelis, but maintain a healthy 11-point lead over their rivals.
Porto are now four points clear in Portugal after they overcame Pacos Ferreira on Friday and Sporting Lisbon prevailed in a five-goal thriller against nearest challengers Benfica.
Sivasspor have established a narrow cushion in Turkey after they emerged with maximum points from a weekend clash with Eskisehirspor and title rivals Galatasaray, Fenerbahce and Trabzonspor all lost.