Fourth-placed Malaga failed to take full advantage of Valencia's setback when they surrendered the lead in the later kick-off and drew 1-1 at home to Real Sociedad, who had Mikel Gonzalez sent off shortly before half-time.
With five matches remaining, Valencia, who play their Europa League semi-final first leg at La Liga rivals Atletico Madrid on Thursday, have 52 points, with Malaga on 51 and fifth-placed Levante, 2-1 losers at home to Barcelona on Saturday, on 48.
In a congested middle section of the table, where only eight points separate Levante from Rayo Vallecano in 14th, Espanyol, Athletic Bilbao, Sevilla and Atletico Madrid all have 45 points.
Atletico are 10th after their 1-0 win at Rayo Vallecano in the late kick-off, Espanyol are ninth and Bilbao, who won 1-0 at home to Real Mallorca, are eighth.
Sevilla, in seventh, can draw level with Levante on 48 points with a win at Getafe on Monday that would also take them above Osasuna. The Pamplona-based club stay sixth on 46 points after they lost 1-0 at Real Betis.
Valencia looked a shadow of the side who have blazed a trail into the semi-finals of Europe's second-tier club competition.
They fell behind in the 26th minute at a sun-bathed and festive Cornella-El Prat stadium when Cristian Gomez powered a Sergio Garcia centre into the net from close range.
Joan Verdu doubled the lead four minutes later with a superb strike from just outside the penalty area that arrowed into the top corner, Alvaro Vazquez added a 58th-minute third after a mix-up in the visitors' defence and Kalu Uche rolled in a fourth around 10 minutes from time.
"We played a poor match and they deserved to win," Valencia coach Unai Emery told a news conference.
"The match was evenly balanced in the opening stages but after their first goal everything went in the opponent's favour and we were a notch below Espanyol," he added.
"Now we need to pick ourselves up and focus on our remaining league games."
At the Rosaleda, ambitious Qatar-owned Malaga were ahead in the 19th minute thanks to Isco's deflected shot before defender Gonzalez earned a second yellow card shortly before half-time.
Xabi Prieto equalised four minutes into the second half and Malaga were unable to breach the visitors' defence again despite numerous chances and the introduction of former Real Madrid and Manchester United striker Ruud van Nistelrooy.
The players were furious when the officials ruled out a Martin Demichelis strike for offside in the dying moments and television replays suggested their complaints were justified.
"They disallowed a legitimate goal and that decided the match," Malaga coach Manuel Pellegrini said at a news conference.
"But winning would not yet have guaranteed us a place in the Champions League and there are 15 points still available and a lot of teams in the mix," added the Chilean.
At the other end of the table, Real Zaragoza's bid to avoid the drop gathered pace when they won 1-0 at home to fellow strugglers Granada, a fourth victory in six games.
Zaragoza have 31 points in 18th, five behind Granada and three ahead of Sporting Gijon, who lost 3-1 at leaders Real Madrid on Saturday.
Racing Santander stay bottom on 26 points after they could only manage a 1-1 draw at 16th-placed Villarreal.
Real will have a four-point advantage over chasing Barca when they meet at the Nou Camp for the second 'Clasico' of the campaign next weekend after the arch rivals' wins on Saturday.
Real, whose Portugal forward Cristiano Ronaldo broke his own Spanish record with his 41st goal of the campaign, came from a goal down to beat Gijon at the Bernabeu.
Two hours later Argentina's World Player of the Year Lionel Messi equalled Ronaldo's mark with both goals in Barca's comeback victory at Levante.
Real's win also meant Jose Mourinho's side matched the club's Spanish record of 107 goals scored in a season set under Welsh coach John Toshack 22 years ago.
Real have 85 points, with Barca, bidding for a fourth straight title, on 81 and Valencia trailing by 28 in third.
If Real and Barca finish level the title will be decided on head-to-head record. Barca currently have the advantage after winning 3-1 in Madrid in December.