The estate of Jean-Michel Charlier, co-creator and original writer of the Blueberry comic book series, found the film's changes to the plot and tone (especially the shamanism storyline) so appalling that they made a request to have Charlier's name removed from the credits.
Val Kilmer was originally offered the headlining role but respectfully declined. Willem Dafoe and Benicio Del Toro were then considered for the role of Mike Blueberry, but Jan Kounen remembered conversations he had about shamanism with his friend Vincent Cassel and chose him instead.
Milla Jovovich was the first choice for the role of Maria but turned it down because of scheduling conflicts.
Jan Kounen originally wanted Vincent Cassel to play the role of Prosit, but reconsidered and cast Eddie Izzard in the part instead
Prosit, the name of Eddie Izzard's character, is the German word for cheers when drinking together.