The Belgian was one of just three Lotto riders left in the race after Roger Kluge abandoned on stage 14 up the Monte Zoncolan but announced on Monday morning that he too would not be continuing on to Milan.
"With tears in my eyes and pain in the knee, I have to say goodbye to the Giro," De Gendt wrote on Twitter before stage 16 kicked off in Sacile.
"I could not perform on my normal level in the last two weeks and there was no improvement. The only right decision that could be made at this moment. I'm sorry to leave my two teammates behind."
Climber Harm Vanhoucke and Italian Stefano Oldani remain in the race for the team, though the squad have had a successful Giro after sprinter Caleb Ewan took two stage wins before withdrawing on stage 8 with knee pain.
"Unfortunately, Thomas De Gendt did not take the start ini Sacile today," the team announced on Twitter. "Thomas' pain in the knee of the last weeks got worse in bad weather at the Giro."
Lotto Soudal's plight at the Giro evokes memories of their 2003 Giro campaign. At that race, Koos Moerenhout rode the final three stages as the sole representative from Lotto-Domo after his last two teammates Nick Gates and Geert Steegmans missed the time limit on the Alpine stage 18 to Chianale.
De Gendt, meanwhile, is expected to return for the Tour de France, while he is also set to compete at the Vuelta a España later in the year to complete a Grand Tour triple.
With tears in my eyes and pain in the knee i have to say goodbye to the Giro. I could not perform on my normal level the last 2 weeks and there was no improvement. The only right decision that could be made at this moment. I’m sorry to leave my 2 teammates behind.May 24, 2021
Thank you for signing up to Cycling News. You will receive a verification email shortly.
There was a problem. Please refresh the page and try again.