Geraint Thomas has withdrawn from the Tirreno-Adriatico during Saturday's fourth stage with "stomach issues".
The Team Sky rider, who became the third Briton to win the Tour de France in July, was 133km into the 221km stage in Italy when he pulled out.
Thomas, 32, began the day 38 places behind overall leader Adam Yates.
Kazakhstan's Alexey Lutsenko crashed twice in the final 20km as he claimed a remarkable stage victory, with Yates finishing third to maintain his lead.
Lutsenko was leading by a minute when he went off course after misjudging a left-hand corner.
He recovered but, with his lead cut, the 26-year-old fell heavily on another turn and was caught by a group including Mitchelton-Scott's Yates.
Despite the fall, Astana rider Lutsenko moved back in front on a sprint with 100m remaining to claim victory in Fossombrone.
The prestigious seven-day race concludes on Tuesday.
Meanwhile, at Paris-Nice, Team Sky's Egan Bernal took over the race lead from team-mate Michal Kwiatkowski after the Pole slipped back in the final 2km of stage seven.
Colombia's Daniel Martinez beat compatriot Miguel Angel Lopez to win the stage at the summit of the Col de Turini, while Britain's Simon Yates was fourth, 20 seconds back, alongside Nicolas Edet in third.
Bernal chased down Philippe Gilbert to claim the leader's yellow jersey and now leads the Belgian by 45 seconds, with Nairo Quintana a second further back, heading into Sunday's final stage.
Tirreno-Adriatico stage four result
1. Alexey Lutsenko (Kaz/Astana) 5hrs 16mins 29secs
2. Primoz Roglic (Slo/Team Jumbo-Visma) Same time
3. Adam Yates (GB/Mitchelton-Scott)
4. Jakob Fuglsang (Den/Astana)
5. Davide Formolo (Ita/Bora-Hansgrohe) +10secs
Tirreno-Adriatico general classification
1. Adam Yates (GB/Mitchelton-Scott) 15hrs 53mins 42secs
2. Primoz Roglic (Slo/Team Jumbo-Visma) +7secs
3. Tom Dumolin (Ned/Team Subweb) +50secs
4. Julian Alaphilippe (Fra/Deceuninck-Quick-Step) +56secs
5. Sam Oomen (Ned/Team Subweb) Same time