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Pedersen fell ill the night before Stage 13 with a cough and sore throat, becoming the latest in a long list of riders to leave the race. With the Dane's withdrawal, 41 of 170 riders have now left with 135 remaining and 10 stages still to race.
Trek-Segafredo confirmed the news of Pedersen's departure in a statement posted to their Twitter account prior to the start of what would turn out to be a heavily reduced Stage 13 to Crans-Montana.
"Unfortunately, we have to report that Mads Pedersen won't take the start at today's stage of the Giro," The statement read.
"Mads had a troubled night with a cough. He woke up this morning with a sore throat and tracheitis and is not fit to race."
It's a cruel end to a race Pedersen had started so well, sprinting to victory on Stage 6 in Naples to make history as the 105th rider ever to win a stage in all three Grand Tours while remaining a consistent contender for the points jersey until his last day.
He was sitting in second just 24 points behind leader Jonathan Milan (Bahrain-Victorious) after picking up 12 points from the intermediate sprint in the Stage 12 breakaway group.
Pedersen will now have more time than expected to recover and begin preparing for the Tour de France in July, where he won Stage 13 at Saint-Etienne in last year's edition.
The Giro d'Italia continues tonight with Stage 14, a 193 kilometre mostly flat day from Sierre to Cassano Magnago. Watch the action from 7:55pm AEST on SBS VICELAND and SBS On Demand.