Despite missing injured duo Pedri and Ousmane Dembele, Xavi rested other important players in the 1-0 defeat by Almeria on Sunday, prioritising the Clasico cup clash and spurning the chance to stretch their league lead to 10 points on Madrid.
Adding to Barca's unease ahead of the Clasico, top scorer Robert Lewandowski has suffered a hamstring strain and is set to miss out, although Ansu Fati is poised to return.
Delivering what Xavi described as the "worst performance of the season" at Almeria, Barcelona suffered their second consecutive defeat after they were knocked out of the Europa League by Manchester United at Old Trafford.
A third defeat at the Santiago Bernabeu could send the team into a spiral, with their seven-point La Liga lead strong but not unassailable.
The Catalans visit the Santiago Bernabeu a day after Osasuna welcome Athletic Bilbao to El Sadar in the other Copa del Rey semi-final first leg.
"We have to change our mindset if we want to win the league and the cup," warned Xavi after El Bilal Toure's goal inflicted only their second Liga defeat of the season.
"We have no excuse, we didn't show the desire to play, intensity, that is what worries me the most.
"You can slip up, but you have to show passion and desire and in the first half we lacked that."
Anything other than a good result in the capital will raise further questions about the coach's decision to rest Ronald Araujo, Jules Kounde, Raphinha and Alejandro Balde against Almeria.
- Instant results -
Xavi has said if his team win La Liga but not the Copa del Rey it would still count as a good season, with the Spanish Super Cup already in the bag.
However, losing this double-header against their arch-rivals would allow further doubts about the project to creep in, fuelling Xavi's detractors after spending big last summer.
Barcelona brought in several players, including striker Robert Lewandowski from Bayern Munich as well as Kounde and Raphinha, and the outlay they made and the financial manoeuvring they did to get the transfers through demands instant results.
Real Madrid saw their disappointing derby draw against Atletico on Saturday transformed into a better result by Barcelona's stumble.
With one foot in the Champions League quarter-finals after an emphatic 5-2 win over Liverpool at Anfield, Carlo Ancelotti's side can turn their attention to getting revenge after their Spanish Super Cup humbling.
Barcelona ran out emphatic 3-1 winners in Saudi Arabia in January as they won the first trophy of the Xavi era.
On that day, the Catalans, desperate to end their silverware drought, seemed far more up for the fight than Madrid but the Copa del Rey is a different story.
The last time Madrid lifted the trophy was a 3-1 win over Barcelona in the 2014 final at Mestalla, when Gareth Bale scored a magnificent solo goal.
Los Blancos are without injured trio David Alaba, Rodrygo and Ferland Mendy.
"Now the Cup is the most important thing because it's the next game and we are very close to a title," said Carlo Ancelotti after Madrid's derby draw.
"We're 270 minutes away from winning a title."
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