Alexandre Vinokourov and Andreas Kloden - both leading contenders for the Tour de France - were left struggling after crashes on stage five.
Vinokourov appeared to have injured his hip and knee
Vinokourov lost 80 seconds to yellow jersey holder Fabian Cancellara while German Kloden fractured his tailbone in a fall midway through the day.
Italian Filippo Pozzato took the stage victory from Oscar Friere in a sprint.
Sylvain Chavanel secured the King of the Mountains jersey after a 154km breakaway over seven climbs.
Pozzato's pace, and the accompanying 20-second bonus, moved him to third in the overall standings.
Veteran Erik Zabel finished fifth to take the green jersey from Tom Boonen, one of a clutch of sprinters left behind by the pack on the eighth and final climb of the day over the Cote de la Croix de la Liberation.
It would be a pity to lose the Tour like that, but life goes on
It was a day of spills as Vinokourov's Astana team-mate Kloden - currently second in the standings - tumbled into a ditch 107km into the stage, a 182.5km ride from Chablis to Autun.
Vinokourov needed stitches in a deep cut on his right knee after his chain snapped on the way down from the category-two Haut-Folin - the penultimate climb of the day.
His team dropped back to pace him back to the main group but struggled as the gradient increased and he could not move on from the trailing group, which included Boonen.
Asked if he was concerned about team leader Vinokourov, Astana manager Marc Biver said: "He is a warrior, I'm not too worried.
"If these kind of accidents prevent us from contending for overall victory, then we'll put it down to fate. There's not much we can do about that.
"It would be a pity to lose the Tour like that, but life goes on."
Team spokeswoman Corinne Druey said of Kloden: "The diagnosis is a fissure in his coccyx.
"He had already broken this bone three years ago so it is more fragile than usual.
"It is very painful. If he doesn't have a bad night he should start Friday's stage."
Pozzato was reticent afterwards, saying: "I'm sorry, because when I knew that Vinokourov had fallen, I was tempted to ask my team to slow down and wait for him.
"Maybe there is less respect for the big riders than there once was.
"When I started in cycling there was a very clear hierarchy and I was afraid to get too close to [Lance] Armstrong... I always stayed three metres back and never got too close."
There was excitement from the start of the day as Chavanel, William Bonnet and Gianpaolo Cheula, who attacked 19km out from the start in Chablis, were joined by Gilbert soon afterwards.
Chavanel and Gilbert were finally overhauled by the main pack on the final climb.
Several riders, including Briton David Millar, then tried their luck in attacking without success before the final sprint.
Millar stays fourth in the general classification, but compatriot Bradley Wiggins tumbled out of the top 10 and lost 99 places in the rankings after coming in almost five minutes back.
Chavanel took maximum points from seven climbs in all, moving well clear of previous holder Stephane Auge in the rankings for the polka dot jersey.
There will be little movement in that contest on Friday as the 189km stage from Semur-en-Auxois to Bourg-en-Bresse involves just two small climbs. But the gradient goes sharply upwards on Saturday as it arrives in the Alps.
Stage five result:
1. Filippo Pozzato (Ita) Liquigas 4 hr 39 min 1 sec
2. Oscar Freire (Spa) Rabobank @ 0 secs
3. Daniele Bennati (Ita) Lampre-Fondital @ 0 secs
4. Kim Kirchen (Lux) T-Mobile @ 0 secs
5. Erik Zabel (Ger) Milram @ 0 secs
6. George Hincapie (US) Discovery Channel @ 0 secs
7. Cristian Moreni (Ita) Cofidis @ 0 secs
8. Stefan Schumacher (Ger) Gerolsteiner @ 0 secs
9. Bram Tankink (Ned) Quick-Step @ 0 secs
10. Jerome Pineau (Fra) Bouygues Telecom @ 0 secs
37. David Millar (GB) Saunier Duval @ 0 secs
83. Alexandre Vinokourov (Kaz) Astana @ 1 min 20 secs
149. Bradley Wiggins (GB) Cofidis @ 4 mins 57 secs
159. Charlie Wegelius (GB) Liquigas @ 11 mins 15 secs
172. Geraint Thomas (GB) Barloworld @ 11 mins 15 secs
181. Mark Cavendish (GB) T-Mobile @ 18 mins 32 secs
1. Fabian Cancellara (Swi) Team CSC 24 hr 28 min 56 sec
2. Andreas Kloeden (Ger) Astana @ 33 secs
3. Filippo Pozzato (Ita) Liquigas @ 35 secs
4. David Millar (GB) Saunier Duval @ 41secs
5. George Hincapie (US) Discovery Channel @ 43 secs
6. Vladimir Gusev (Rus) Discovery Channel @ 45 secs
7. Vladimir Karpets (Rus) Caisse d'Epargne @ 46 secs
8. Mikel Astarloza (Spa) Euskaltel @ 49 secs
9. Thomas Dekker (Ned) Rabobank @ 51 secs
10. Benoit Vaugrenard (Fra) Francaise des Jeux @ 52 secs
81. Alexandre Vinokourov (Kaz) Astana @ 2 mins 10 secs
105. Bradley Wiggins (GB) Cofidis @ 5 mins 40 secs
154. Geraint Thomas (GB) Barloworld @ 12 mins 22 secs
159. Charlie Wegelius (GB) Liquigas @ 12 mins 31 secs
182. Mark Cavendish (GB) T-Mobile @ 22 mins 29 secs