The Blaugrana and Real Madrid will meet on Saturday afternoon in the league, just days after Jose Mourinho's men emerged victorious from their Tuesday night Copa del Rey semi-final.
The stakes are, however, very different this time around with the Calatans enjoying a 12-point lead at the top of the table.
But Del Bosque told Marca: "Every Clasico is different.
"Barcelona are playing to tighten their grip on the championship and so it will be an important match for them.
"For Real Madrid they have not lost all hopes in the league and for this reason it will be important for them also."
Del Bosque also spoke about the venue for the Copa del Rey final between Real Madrid and Atletico Madrid, with the Spain boss sure it will take place in Spain's capital.
"All the circumstance surrounding this match indicate it will be played in Madrid," he added.
"Furthermore, the Madrid football federation will be celebrating its anniversary so it would be a fitting act of celebration."