Promoted Numancia are the only side to have beaten Barcelona in the Primera Liga this season and they have the chance to complete an unlikely double over the runaway leaders at the Nou Camp on Saturday.
Pep Guardiola's first league game in charge of Barca ended with a 1-0 defeat in Soria on August 31, but they have since gone on to collect a record number of points for the first half of a season with 50 from a possible 57.
For modest Numancia, their opening day victory marked a high point in their campaign and since mid-September they have been in the bottom half of the standings. They lie 17th, five points above the relegation places.
"Fortune was on our side (when we beat Barca)," Numancia defender Juanra said on the Marca website.
"We have to believe (we can get something positive from Saturday's game). Anything can happen in football."
Their wily Croatian coach Sergio Kresic will have been impressed with the way struggling Espanyol held Barca to a goalless draw in a Copa del Rey quarter-final first leg on Wednesday.
But Guardiola fielded a weakened side at Montjuic and will have rested first-team regulars such as Samuel Eto'o, Thierry Henry and Daniel Alves back on Saturday.
Second-placed Real Madrid also suffered an opening day defeat, losing 2-1 away to Deportivo Coruna, but cannot afford further slip ups as they look to close the 12-point gap on Barca.
Juande Ramos's side, who host Depor at the Bernabeu on Sunday, have tightened up in defence of late and have won four on the trot.
"It is going to be difficult (to catch Barca), but I am sure they will have a dip in form and that will be when the current league champions step forward," Real striker Gonzalo Higuain said.
Depor have slipped down to eighth and have lost their last four matches in all competitions.
Atletico Madrid's poor start to the new year has seen them slide down to sixth and they are still seeking their first win of 2009 in five attempts.
On Sunday, they visit in-form Malaga who have drawn level on points, but are seventh on goal difference.
Atletico beat promoted Malaga 4-0 in the Calderon at the start of the season and midfielder Apono pointed out the Andalucians were still annoyed by that setback.
"I can't forget it. We have a huge determination to do the same to them, but a win by one goal would do," he said.