La Liga leaders Real return to domestic action after the mid-season break looking to extend their superb stretch of 22 consecutive competitive victories - a Spanish record.
However, in Valencia - who this week announced the signing of Enzo Perez from Benfica - they meet a side with lofty ambitions of their own and Nuno Espirito Santo's men occupy the final UEFA Champions League berth in La Liga.
Moreover, only Barcelona have left Valencia with maximum points this term and goalkeeper Diego Alves is hoping that the atmosphere at the Mestalla can help halt Carlo Ancelotti's side in their tracks.
"It's a great game," he told Valencia's official website. "They are fighting for the league [but] on our own pitch we are very strong.
"The crowd is a plus and with them Valencia are much stronger."
Stopping Real's domestic dominance this term is becoming increasingly difficult, but Luis Enrique's Barcelona side remain in pole position to do so ahead of a trip to Real Sociedad.
The Catalans will need no reminding of the test that awaits them at Anoeta having lost last season's corresponding fixture 3-1.
Sociedad have also proved an increasingly difficult side to beat since David Moyes took the reins in November and the Scot will be desperate to claim a huge scalp and move up the Liga table.
Also on Sunday, Getafe and Espanyol have home matches with Rayo Vallecano and Eibar.
Champions Atletico Madrid, who are third, will kick off 2015 in La Liga in Saturday's early kick-off against Levante.
Diego Simeone's men have been boosted by the return of fans' favourite Fernando Torres on an 18-month loan from Milan, although the Spain international striker is ineligible until January 5 when the Italian transfer window opens.
At the other end of the table strugglers Cordoba and Granada, who sit in the relegation zone, meet at the Estadio Nuevo Arcangel on Monday.
Only Cordoba - who this week terminated the contract of striker Mike Havenaar - have won fewer matches than Granada's tally of two games.
But full-back Daniel Pinillos is confident of a morale boosting win.
"It's an important game," he said. "All matches are finals and the team is confident of getting the three points against Granada."
The likes of Deportivo La Coruna and Almeria could drop into the bottom three by the end of the round of fixtures, the former host Athletic Bilbao while the latter visit Malaga on Saturday.
Saturday also sees Sevilla host Celta Vigo, while fellow UEFA Champions League hopefuls Villarreal hit the road to play bottom club Elche.
