Barcelona face another serious question of their credentials this weekend as they travel to high-flying Sevilla.
Real Madrid have a contrasting task in hosting lowly Leganes, while Atletico Madrid and Villarreal will look to keep pace as they also attempt to avoid upsets.
Sevilla v Barcelona (Sunday, 7.45pm, Sky Sports 1HD)
The La Liga champions travel to Andalucia on the back of a 3-1 defeat to Manchester City, having had their defensive vulnerabilities exposed by Pep Guardiola's side, but in retrospect they had it coming.
Their form had looked questionable, with a last-gasp winner at struggling Valencia followed by a narrow 1-0 win against bottom club Granada at the Nou Camp.
The absence of key trio Andres Iniesta, Jordi Alba and Gerard Pique has hit Barca hard, and Luis Enrique will be desperate to have the latter duo back for what could be a crucial clash.
Their hosts have arguably been the over-performers of the season, sitting third after losing just one of their first 10 games and claiming the significant scalp of Atletico Madrid a fortnight ago.
That was an extension of some formidable form at home, with maximum points claimed in 19 of their last 22 matches at the Ramon Sanchez Pizjuan, including a 100 per cent record this season.
The arrival of Samir Nasri has had a huge impact and provided the quality to go with the intense pressing style that manager Jorge Sampaoli has imposed on his new side.
Despite all of the above, Barca are considered odds-on favourites with Sky Bet, who make Sevilla 19/5 to make it six wins from six at home and really announce themselves as genuine title contenders.
Prediction: Sevilla to win and both teams to score - 6/1 with Sky Bet
Real Madrid v Leganes (Sunday, 11am, Sky Sports 3HD)
Much like their great rivals, significant question marks surround Real Madrid after 10 games, with defensive absentees also hampering them.
Zinedine Zidane's men do, however, still sit top of La Liga and are unbeaten in all competitions, so talk of a crisis is some way off, but a failure to keep a clean sheet in any of their last 10 games is cause for concern.
They had actually only conceded once in each of their four successive wins heading into the midweek Champions League action, but a 3-3 draw at Legia Warsaw has got alarm bells ringing.
Some might point to the inclusion of back-up player Nacho in Pepe and Sergio Ramos' absence, but Zidane's reluctance to protect his backline with a holding midfielder is perhaps the greater issue.
The French legend started two strikers, Karim Benzema and Alvaro Morata, along with two attacking-midfielders and Gareth Bale and Cristiano Ronaldo in Poland. If there's an 'all-out attack' button in real management then Zidane has had it switched on.
However, Leganes hardly look poised to exploit any defensive vulnerabilities on Sunday, having lost their last three, conceding nine goals, and failing to score in their last two.
Prediction: Real Madrid to win and over 4.5 goals - 5/6 with Sky Bet
Elsewhere....
Sunday's second fixture promises to be an intriguing one, with two sides enduring contrasting fortunes meet at the Balaidos.
Celta Vigo are proving to be Spain's entertainers, with no less than four goals in each of their last six games in all competitions, while Valencia are showing signs of dragging themselves out of the mire under Cesare Prandelli.
The other 3.15pm kick-off sees Athetic Bilbao travel to Espanyol, while Villarreal will look to bounce back from successive humiliating defeats to Eibar and Osmanlispor when they host Real Betis in the 5.30pm kick-off.
Saturday's action predominantly involves showdowns between the league's strugglers, although Real Sociedad versus Atletico Madrid both hold lofty aspirations.
Interestingly, Diego Simeone's tactics seem to have switched depending on location with his side proving more expansive at home and back to their stringent selves on the road, conceding just twice in seven trips.
The day's opening two clashes are likely to have significant say on the relegation battle as four of the bottom six are involved, while Las Palmas and Eibar will look to continue to punch above their weight in the late kick-off, having defied modest expectations to sit 10th and eighth respectively.