Fabian Cancellara retained his overall lead in cycling's premier event, but some of those expected to challenge for the championship lost significant time due to the pileup. They included Frank Schleck, Alejandro Valverde and Mark Cavendish.
Three men had to abandon the race completely with injuries suffered in the crash.
Sagan won a sprint at the end of the Epernay-to-Metz stage, a 205-kilometer ride that took 4 hours, 37 minutes to complete. Andre Greipel, who had won the previous two stages, was second and Matthew Harley Goss was third.
Sagan, Greipel and the other sprinters are expected to fade from the scene Saturday when the Tour heads into the mountains for a 199-kilometer journey from Tomblaine to La Planche del Belles Filles.