Twenty-one teams, containing a total of 168 riders, participated in the race:[2][3] The prologue stage saw 2005 GC winner Bobby Julich retain the yellow/white GC leader's jersey after defeating Kazakh Andrey Kaschechkin, who held the best time through most of the stage's duration, by a narrow margin of 1 second.

After a short solo breakaway effort by David Zabriskie, Frenchmen Cristophe Laurent and Stéphane Augé launched a long attack at the 60-km point but were caught by the chasing peloton only 2 km before the finish line.

The polka-dotted mountains jersey changed hands due to a long breakaway by French rider Nicolas Crosbie, who established a maximum lead of 27'30" after 81 kilometers.

The blue jersey for the best young rider was awarded to Benoît Vaugrenard who took over first place with former leader Alberto Contador finishing 1'13 behind the pack.

In the third stage to Saint-Étienne, where Kazakh racer Andrei Kivilev died after a fall in the 2003 edition of Paris–Nice (prompting the UCI to make the wearing of helmets mandatory during all UCI-sanctioned races), there were some changes to the race classifications as American Floyd Landis took over first place in the GC, placing second in the stage after Patxi Xabier Vila Errandonea.