Barcelona took full advantage of Real Madrid's shock defeat against Getafe to open up a five point lead over their Clasico rivals after only two games in La Liga.
Real's defence of their title began with a stutter with a draw against Valencia at the Santiago Bernabeu last weekend, and now a loss away from home to Getafe has handed Barcelona the immediate initative.
Add to these results Barcelona's triumph in the first leg of the Super Copa on Thursday, and Real are without a victory so far this season and must rally quickly to ensure they do not fall further off the pace.
Gonzalo Higuain had given Los Blancos the lead at the Coliseum Alfonso Perez, but Juan Valera's header restored parity before Abdelaziz Barrada condemned the champions to a surprise loss.
Barcelona, however, hardly had it all their own way against Osasuna and had to work hard to grind out a win and move themselves to the top of the table.
Joseba Llorente gave Osasuna an unexpected 17th-minute lead before a brace from the already free-scoring Lionel Messi ensured Tito Vilanova's side maintained a 100 percent record in La Liga so far.