Australian Simon Gerrans has broken his wrist and French rider William Bonnet needs quick surgery for a fracture in his neck after a horrendous high-speed crash forced six Tour de France competitors to quit the race.
Gerrans, Bonnet and Swiss Fabian Cancellara are among those who withdrew following the serious incident just over 100km into the third stage, won by Joaquim Rodriguez.
Chris Froome, the 2013 champion, took second on the crash-marred stage over 159.5km from Antwerp to the infamous Mur (wall) de Huy in Belgium.
Cancellara, who started the stage as leader, broke two vertebrae in his back in the crash, which involved 20 riders, but gingerly soldiered on before conceding the leader's yellow jersey to Froome, who holds a one-second advantage over Tony Martin.
Cancellara was visibly hurt, but battled until the finish line, losing 12 minutes on the leaders, before X-rays revealed the extent of the damage.
It was more Tour heartache for the Orica GreenEdge leader Gerrans, who last year was taken out by Mark Cavendish in the sprint finish on the first stage and had to abandon there and then.
This year and racing in his 10th tour the 35-year-old fared only slightly better in making it only to the third stage, compounding his horror season already dogged by five crashes.
"He's fractured his wrist," Orica GreenEdge director Matt White told Fox Sports.
"He's going to need surgery over the next couple of days, and it's very very disappointing for him.
"It's very disappointing for anyone to have to pull out of the Tour de France, but he's had a nightmare of a year with injury.
"Hopefully this is the last of it because he's had more bad luck this year than I think he's had his whole career."
Gerrans' fellow Australian and Orica teammate Michael Matthews was also affected, coming home last more than 21 minutes after the winner.
On a straight road in clear conditions with bright sunshine, FDJ rider Bonnet clipped the wheel of Warren Barguil in front and went down suddenly, causing a ripple through the peloton.
Such was the seriousness of the crash that organisers immediately neutralised the race for a short spell as medics and team officials tended to the injured.
"It was certainly one of the most hectic days I've seen, and a lot of guys were involved in that crash," White said.
"No-one likes to see crashes in general, but it was a high-speed crash and there's no soft landing at that sort of speed.
Bonnet suffered a multi-fragmented fracture of his second cervical vertebra and will be quickly transferred to Paris for surgery to stabilise his neck, an FDJ team statement said.
"One of the French riders from FDJ is not in a good way," White said.
"At the moment it looks like he's in a coma, and fingers crossed that he's going to recover from that injury because we're a very close-knit community in cycling."
Orica bore the brunt of the bad luck, with five riders hitting the deck including South African Daryl Impey who exited the race after fracturing his collarbone.
Tom Dumoulin of the Netherlands and Russian Dmitry Kozontchuk were also forced out due to the injuries they suffered in the same crash.
Froome gained 11 seconds on his overall rivals, defending champion Vincenzo Nibali and Nairo Quintana, while Alberto Contador lost 18sec.
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