Sagan started the race in Siena on Saturday morning and said he was riding to win. However, he suffered on the early climbs and sectors of dirt road, eventually quitting the race with 70km to go. He climbed into a Bora-hansgrohe team car after the seventh sector of dirt road.
"I haven’t been feeling well for the past three days, and when I woke up this morning I was feeling weak and had a sore throat," Sagan said in a statement released by the team after the race. "However, the Strade Bianche is a prestigious race and I started today out of respect for the thousands of Italian fans who came to watch.
"I started and tried to do my best and race as much as I could," Sagan said. "Around 75km after the start, I got tangled in a big pile-up and suffered a deep cut in my finger that will probably require a couple of stitches, as well as a hit to my left knee. I went on, but at 95km I decided to retire."
Sagan finished fourth last year and has twice been second at Strade Bianche. He was expected to clash with Greg van Avermaet (BMC) and the other big-name riders after impressing in Belgium last week with his second place at Omloop Het Nieuwsblad and then victory at Kuurne-Brussel-Kuurne.
The Bora-Hansgrohe team said via social media that Sagan has been feeling unwell before the start of the race but wanted to ride as much of it as possible despite being under the weather.
Sagan is expected to stay in Italy to recover from his problems before riding Tirreno-Adriatico, which starts on the Tuscan coast on Wednesday.
"My decision wasn’t due to the crash, but simply because I wasn’t feeling well," he said. "I hope to recover as soon as possible and be able to perform at my best in the upcoming races."