The Dutchman had already taken back-to-back victories on stages two and three, but has left the race due to a minor cold, his team have confirmed.
Alpecin-Fenix said the 26-year-old had caught a mild illness while racing through some tough weather conditions in Switzerland, with Van der Poel opting to leave the race to recover for his upcoming goals.
A statement from the team, released ahead of stage six, said: “After the rainfall from the past days, Mathieu van der Poel is suffering from a mild cold.
"While he was looking forward to the next stages, the team’s medical staff decided to pull him out of the Tour de Suisse so as not to compromise his health in light of his next goals.”
Van der Poel, the reigning cyclocross world champion and former Tour of Flanders winner, was using the Tour de Suisse as preparation for his debut in the Tour de France later this month.
During his first Grand Tour, Van der Poel has set himself the goal of winning a stage in this year’s Tour, before he turns his attention to the Tokyo Olympics where he hopes to compete for a medal on the mountain bike.
Van der Poel looks to be in stellar form heading into the Tour, as he dominated the first two road stages of the Tour de Suisse.
On stage two, Van der Poel forced a breakaway late in the day and was able to outsprint Max Schachmann (Bora-Hansgrohe) to take his first victory.
The following day, Van der Poel took a bunch sprint on another Classics-style day, overpowering Christoph Laporte (Cofidis) and Julian Alaphilippe (Deceuninck - Quick-Step) to secure his second win.
His mountain bike preparation has also looked promising, as he won two short track events in recent mountain bike World Cup rounds, and finished second to Tom Pidcock in the XCO event in Nove Mesto.
Thank you for reading 5 articles this month* Join now for unlimited access
Enjoy your first month for just £1 / $1 / €1
*Read 5 free articles per month without a subscription
Join now for unlimited access
Try first month for just £1 / $1 / €1