Tom Dumoulin will not be fit enough to compete in the Tour de France, while four-time champion Chris Froome is set to leave hospital following his horror crash last week.
Team Sunweb confirmed Dumoulin's disappointing news on Thursday – the same day that Froome tweeted to say his goodbyes to the Saint-Etienne hospital that cared for him after his accident at the Criterium du Dauphine.
Dumoulin, the 2017 Giro d'Italia champion and three-time stage winner on the Tour, will be absent from this year's edition after failing to recover sufficiently from the knee injury that forced him into an early withdrawal from the 2019 Giro.
"The last month has been extremely difficult overall, and with the setbacks in the knee recovery," Dumoulin said.
"After what happened at the Giro I really wanted to go for it in the Tour, but this week I realised it's just not realistic for my level to be there in time.
"I've tried so hard to get there but I really have to listen to my body and release myself from chasing an unrealistic goal."
Froome, meanwhile, is starting out on the long road to rehabilitation, having suffered fractures to his leg, elbow and ribs when he took his hands off his bike to blow his nose and hit the wall of a house during a recon run ahead of stage four of the Criterium.
"As my time at @ChuSaintEtienne has come to an end, I'd like to take the opportunity to thank the doctors & nurses for the exceptional care provided to me," the Team INEOS rider posted on Twitter. "It's been a rough week but I appreciate you having made it as comfortable as possible for me.
"This is just the first step to what will be a long recovery. Unfortunately I'm not yet able to go home, but at least I'll have an opportunity to get a visit from my kids."