Valencia, like the rest of La Liga, looks place side could make a statement Saturday against the leaders.
Valencia welcomes Real Madrid, which sits atop the league with a three-point lead over Barca and a four-point lead over Valencia, to the Mestalla for a key league match.
While Real and Barcelona are expected to be in a two-way fight for the Spanish title, Valencia did manage a draw against Barca in league play this season and also tied English power Chelsea in the Champions League.
"Real Madrid are one of the best teams in the world," Valencia defender Adil Rami said, "but we can do to them what we did to Chelsea and Barcelona."
Valencia has yet to lose at home in six matches, winning four of those, and it hopes to add another negative result to Real's away record. Real has its only loss and draw on the road so far in six games away from the Bernabeu.
However, Real has won eight straight La Liga games and 10 in all competitions, and star Cristiano Ronaldo has been in top form again this season.
He has 13 La Liga goals this season, second only to Barca's Lionel Messi, and continued the outburst internationally this week.
Ronaldo scored a pair of goals to seal Portugal's spot in the Euro 2012 finals with a 6-2 win against Bosnia-Herzegovina on Tuesday. The teams tied the first leg, 0-0, but now Ronaldo can relax and focus on La Liga.
Jose Mourinho could shuffle his lineup after the international break as nearly all of his best players were away with their respective national teams, but he has plenty of depth.
Gonzalo Higuain follows Ronaldo on the league scoring charts with 12 goals and Karim Benzema has six.
Rami, Benzema's French teammate, knows a big test awaits Valencia this week as it puts its three-game winning streak on the line, but he looks forward to big challenges in his first season in Spain.
"I'm came here to the best league in the world," Rami said, "to play in games like this one."
Valencia has finished third the last two seasons behind Barca and Real, and it looks like the only squad capable of threatening their dominance this season. For Real, it's important to maintain its edge over Barca.
Barcelona has dropped eight points with four draws, but as the only undefeated side left in Spain and the reigning European champion, it remains the club to beat.
Barca hosts struggling Real Zaragoza on Saturday, when Villarreal hopes to get just its third win of the season when it hosts Real Betis, which is winless in seven since opening the season with four straight wins.
On Sunday, Real Sociedad hosts Espanyol, Osasuna hosts Rayo Vallecano, Sevilla hosts Bilbao, Sporting Gijon hosts Getafe, Atletico Madrid hosts Levante, and Granada hosts Mallorca. On Monday, Racing hosts Malaga