Degenkolb abandoned Paris-Nice with bronchitis and has not recovered in time to start the 291km race on Saturday. Nizzolo dropped out of Tirreno-Adriatico with knee pain, and the team decided not to risk further injury.
"It is with a heavy heart I have to cancel my start at Milan-San Remo as I am still fighting this sickness and wouldn't be fit for the Primavera," Degenkolb said. "I am feeling already better in the last days and will be back on my bike soon. So, no worries for the rest of the Classics season. I wish my team the best for Saturday."
American Kiel Reijnen will step in for Degenkolb, while Boy van Poppel will ride in place of Nizzolo.
In 2017, Nizzolo spent the first months of the year battling tendinitis in his knee. He came back at the Tour of Croatia and raced 10 stages of the Giro d'Italia before succumbing to the injury again. One more fitful restart in the Hammer Series ended badly, but the Italian seemed to be back to health in the Vuelta a San Juan, where he scored a stage win. After such a frustrating year, the Italian is not keen to take any risks.
"I am very, very disappointed that I cannot start Milan-San Remo. It was the biggest goal for me for the first part of the season. So not to start is really sad for me," Nizzolo said.
"We decided not to start because the knee pain has improved but not enough, and we don't want to take any risk for the rest of the season. It's a long race, and it can make more damage. Now we will do everything we can to fix the problem as soon as possible and look forward. I wish all the best to my teammates, and I will be supporting them from in front of the TV. "
The team could still count on budding Classics rider Jasper Stuyven. The 25-year-old Belgian was fourth in last year's Paris-Roubaix and finished just off the podium in Omloop Het Nieuwsblad this year.
Trek-Segafredo for Milan-San Remo: Jasper Stuyven, Fabio Felline, Koen de Kort, Boy van Poppel, Kiel Reijnen, Ryan Mullen, and Gregory Rast.
Click here to subscribe to the Cyclingnews podcast.