Greipel and Matthews are among several riders to have withdrawn ahead of the long 59.4-kilometre individual test against the clock on Saturday. Greipel's team-mate Greg Henderson is also a non-starter with a hard final week in the mountains looming after the time trial.
German champion Greipel won the bunch sprint finish on stage six to Castiglione della Pescaia. He had been hoping for more success in the sprints, but bad weather, bad positioning and crashes held him up.
"The day after the team time trial I had a first chance, but on the uphill finish I started too soon and I got beaten," said Greipel. "Last Tuesday there was a new opportunity, but the escapees stayed ahead and yesterday [Friday] the chaos in the finale was so big that I didn’t get to the front in time to do a good sprint.
"I’m happy we won one stage, but I had hoped for one more."
Greipel is now scheduled to take part in the ZLM Toer with the hope of being selected to ride in the Tour de France in July, where he will face British sprinter Mark Cavendish (Etixx-QuickStep), German Marcel Kittel (Giant-Alpecin), on-form Norwegian Alexander Kristoff (Katusha) and last year's green jersey winner, Peter Sagan (Tinkoff-Saxo).
Matthews won stage three whilst in the overall race lead after his Orica-GreenEdge squad had clinched the opening team time trial.
Saturday's time trial stage is set to lead to a major shake-up in the general classification, which was unexpectedly changed after yesterday's pan-flat stage. Fabio Aru (Astana) took the race lead from Alberto Contador (Tinkoff-Saxo) after Contador was caught up in a crash just outside three kilometres to go.
Team Sky leader Richie Porte was another caught up in the incident, which all but finished his hopes of a high placing in the general classification as he slips to 17th overall, five minutes and five second down on Aru.
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